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Chapter 1 - The normal lung: histology, embryology, development, aging and function

Published online by Cambridge University Press:  05 June 2014

By
Neil Sahasrabudhe ,
John R. Gosney  and
Philip Hasleton
Edited by
Philip Hasleton  and
Douglas B. Flieder
Philip Hasleton
Affiliation:
University of Manchester
Douglas B. Flieder
Affiliation:
Fox Chase Cancer Center, Philadelphia
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Summary

Introduction

Knowledge of normal lung anatomy and function is important for the interpretation of lung biopsies and resections. An understanding of different cell structures and functions allows for a greater appreciation of disease states. In addition basic pulmonary embryology explains congenital pulmonary defects. At the other extreme of life, knowledge of how the lung ages is important, not only for consideration of other diseases, such as hiatus hernias with co-existent aspiration, but also because of the world's increasing elderly population.

Development

The key events of pulmonary embryogenesis and postnatal development are discussed in this chapter. For a more detailed account, the reader is referred to two monographs and several review articles.

The events of human lung growth are divided into five continuous stages, based on anatomic and histological characteristics. These are the embryonic, pseudoglandular, canalicular, saccular and alveolar stages (Table 1) (Figures 1 and 2). Airway and vascular development are closely related. The conducting airways are formed in the embryonic and pseudoglandular stages, while gas exchange units characterized by vascularization and reduction of mesenchyme are formed in the canalicular, saccular and alveolar stages.

Type
Chapter
Information
Spencer's Pathology of the Lung , pp. 1 - 40
Publisher: Cambridge University Press
Print publication year: 2000

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References

Hodson, WA (ed.). Development of the Lung, vol. 6, Lung Biology in Health and Disease. New York: Marcel Dekker, 1977.Google ScholarPubMed
Burri, PH.Lung development and angiogenesis. In Gaultier, C, Bourbon, JR, Post, M, eds. Lung Development. New York: Oxford University Press, 1999. pp. 122–51.CrossRefGoogle Scholar
Chinoy, MR.Lung growth and development. Front Biosci 2003;8:d392–415.CrossRefGoogle ScholarPubMed
Joshi, S, Kotecha, S.Lung growth and development. Early Hum Dev 2007;83:789–94.CrossRefGoogle ScholarPubMed
Hislop, AA.Airway and blood vessel interaction during lung development. J Anat 2002;201:325–34.CrossRefGoogle ScholarPubMed
Kimura, J, Deutsch, GH.Key mechanisms of early lung development. Pediatr Dev Pathol 2007;10:335–47.CrossRefGoogle ScholarPubMed
Maeda, Y, Davé, V, Whitsett, JA.Transcriptional control of lung morphogenesis. Physiol Rev 2007;87:219–44.CrossRefGoogle ScholarPubMed
Potter, EL, Loosli, CG.Prenatal development of the human lung. Am J Dis Child 1951;82:226–8.Google ScholarPubMed
Jeffrey, PK.The development of large and small airways. Am J Respir Crit Care Med 1998;157:S174–80.CrossRefGoogle ScholarPubMed
Kotecha, S.Lung growth for beginners. Paediatr Respir Rev 2000;1:308–13.Google ScholarPubMed
Kajstura, J, Rota, M, Hall, SR, et al. Evidence for human lung stem cells. N Engl J Med 2011;364:1795–806.CrossRefGoogle ScholarPubMed
Lama, VN, Smith, L, Badri, L, et al. Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts. J Clin Invest 2007;117:989–96.CrossRefGoogle ScholarPubMed
Badri, L, Murray, S, Liu, LX, et al. Mesenchymal stromal cells in bronchoalveolar lavage as predictors of bronchioloitis obliterans syndrome. Am J Respir Crit Care Med 2011;183:1062–70.CrossRefGoogle Scholar
Balinotti, JE, Tiller, CJ, Llapur, CJ, et al. Growth of the lung parenchyma early in life. Am J Respir Crit Care Med 2009;179:134–7.CrossRefGoogle ScholarPubMed
Cooney, TP, Thurlbeck, WM.The radial alveolar count method of Emery and Mithal: a reappraisal 2 – intrauterine and early postnatal lung growth. Thorax 1982;37:580–3.CrossRefGoogle ScholarPubMed
deMello, DE, Sawyer, D, Galvin, N, Reid, LM.Early fetal development of lung vasculature. Am J Respir Cell Mol Biol 1997;16:568–81.CrossRefGoogle ScholarPubMed
deMello, DE, Reid, LM.Embryonic and early fetal development of human lung vasculature and its functional implications. Pediatr Dev Pathol 2000;3:439–49.CrossRefGoogle ScholarPubMed
Burri, PH.Structural aspects of postnatal lung development – alveolar formation and growth. Biol Neonate 2006;89:313–22.CrossRefGoogle ScholarPubMed
Voelkel, NF, Vandivier, RW, Tuder, RM.Vascular endothelial growth factor in the lung. Am J Physiol Lung Cell Mol Physiol 2006;290:L209–21.CrossRefGoogle ScholarPubMed
Langhe, , del Moral, P, Tefft, D, Bellusci, S, Warburton, D.Genetic, molecular and cellular basis of lung development. In Fishman, AP, ed. Fishman's Pulmonary Diseases and Disorders, 4th ed. New York: McGraw Hill Medical, 2007. pp. 81–90.Google Scholar
Chen, H, Zhuang, F, Liu, YH, et al. TGF-beta receptor II in epithelia versus mesenchyme plays distinct roles in the developing lung. Eur Respir J 2008;32:285–95.CrossRefGoogle ScholarPubMed
Tarantal, AF, Chen, H, Shi, TT, et al. Overexpression of transforming growth factor Iz1 in fetal monkey lung results in prenatal pulmonary fibrosis. Eur Respir J 2010;36:907–14.CrossRefGoogle Scholar
Urban, Z, Hucthagowder, V, Schurmann, N, et al. Mutations in LTBP4 cause a syndrome of impaired pulmonary, gastrointestinal, genitourinary, musculoskeletal, and dermal development. Am J Hum Genetics 2009;85:593–605.CrossRefGoogle Scholar
Kho, AT, Bhattacharya, S, Tantisira, KG, et al. Transcriptomic analysis of human lung development. Am J Respir Crit Care Med 2010;1:54–63.CrossRefGoogle Scholar
Becklake, MR, Kauffmann, F.Gender differences in airway behaviour over the human life span. Thorax 1999;54:1119–38.CrossRefGoogle ScholarPubMed
Torday, JS, Nielsen, HC.The sex difference in fetal lung surfactant production. Exp Lung Res 1987;12:1–19.CrossRefGoogle ScholarPubMed
Simard, M, Provost, PR, Tremblay, Y.Sexually dimorphic gene expression that overlaps maturation of type II pneumocytes in fetal mouse lungs. Reprod Biol Endocrinol 2006;4:25–38.CrossRefGoogle Scholar
Ranganathan, S.Lung development, lung growth and the future of respiratory medicine. Eur Respir J 2010;36:716–7.CrossRefGoogle ScholarPubMed
Linnane, BM, Hall, GL, Nolan, G, et al. Lung function in infants with cystic fibrosis diagnosed by newborn screening. Am J Respir Crit Care Med 2008;178:1238–44.CrossRefGoogle ScholarPubMed
Sly, PD, Brennan, S, Gangell, C, et al. Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening. Am J Respir Crit Care Med 2009;180:146–52.CrossRefGoogle ScholarPubMed
Laughon, M, O'Shea, MT, Allred, EN, et al. Chronic lung disease and developmental delay at 2 years of age in children born before 28 weeks' gestation. Pediatrics 2009;124:637–48.CrossRefGoogle Scholar
Hancox, RJ, Poulton, R, Greene, JM, McLachlan, CR, Pearce, MS, Sears, MR.Associations between birth weight, early childhood weight gain and adult lung function. Thorax 2009;64:228–32.CrossRefGoogle ScholarPubMed
Wailoo, MP, Emery, JL.Normal growth and development of the trachea. Thorax 1982;37:584–7.CrossRefGoogle ScholarPubMed
Schittney, JC, Burri, PH.Development and growth of the lung. In Fishman, AP, ed. Fishman's Pulmonary Diseases and Disorders, 4th ed. New York: McGraw Hill Medical, 2007. pp. 100–14Google Scholar
Balinotti, JE, Tiller, CJ, Llapur, CJ et al. Growth of the lung parenchyma early in life. Am J Crit Care Med 2009;179:134–7.CrossRefGoogle ScholarPubMed
Thurlbeck, WM.Postnatal human lung growth. Thorax 1982;37:564–71.CrossRefGoogle ScholarPubMed
Cooney, TP, Thurlbeck, WM.The radial alveolar count method of Emery and Mithal: a reappraisal 1 – postnatal lung growth. Thorax 1982;37:572–9.CrossRefGoogle ScholarPubMed
Raiser, DM, Kim, CF.Commentary: Sca-1 and cells of the lung: a matter of different sorts. Stem Cells 2009;27:606–11.CrossRefGoogle ScholarPubMed
Dor, Y, Stanger, BZ.Regeneration in liver and pancreas: time to cut the umbilical cord?Sci STKE 2007;414:pe66.Google Scholar
Rawlins, E.Lung epithelial progenitor cells; Lessons from development. Proc Am Thorac Soc 2008;5:675–81.CrossRefGoogle ScholarPubMed
Driscoll, B, Buckley, S, Bui, KC, Anderson, KD, Warburton, D.Telomerase in alveolar cell development and repair. Am J Physiol Lung Cell Mol Physiol 2000;279:L1191–8.CrossRefGoogle Scholar
Warburton, D, Perin, L, DeFilippo, R, Bellusci, S, Shi, W, Driscoll, B.Stem/Progenitor cells in lung development, injury repair and regeneration. Proc Am Thorac Soc 2008;5:703–6.CrossRefGoogle ScholarPubMed
Kim, CF, Jackson, EL, Woolfenden, AE, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005;121:823–35.CrossRefGoogle ScholarPubMed
Verbraecken, JA, De Backer, WA.Upper airway mechanics. Respiration 2009; 78:121–33.CrossRefGoogle ScholarPubMed
Mukhopadhyay, S, Katzenstein, AA.Pulmonary disease due to aspiration of food and other particulate matter: a clinicopathologic study of 59 cases diagnosed on biopsy or resection specimens. Am J Surg Pathol 2007;31:752–9.CrossRefGoogle ScholarPubMed
Warren, WH, Milloy, FJ.Pulmonary vascular system and pulmonary hilum. Thorac Surg Clin 2007;17:601–17.CrossRefGoogle ScholarPubMed
Ugalde, P, Camargo, JdeJ, Deslauriers, J.Lobes, fissures and bronchopulmonary segments. Thorac Surg Clin 2007;17:587–99.CrossRefGoogle ScholarPubMed
de la Grandmaison, GL, Clairand, I, Durigon, M.Organ weight in 684 adult autopsies: new tables for a Caucasoid population. Forensic Sci Int 2001;119:149–54.CrossRefGoogle ScholarPubMed
Medlar, EM.Variations in interlobar fissures. Am J Roentgenol 1947;57:723–5.Google ScholarPubMed
Raasch, BN, Carsky, EW, Lane, EJ, O'Callaghan, JP, Heitzman, ER.Radiographic anatomy of the interlobar fissures: a study of 100 specimens. Am J Roentgenol 1982;138:1043–9.CrossRefGoogle ScholarPubMed
Mahmut, M, Nishitani, H.Evaluation of pulmonary lobe variations using multidetector row computerized tomography. J Comput Assist Tomogr 2007;31:956–60.CrossRefGoogle Scholar
Meenakshi, S, Manjunath, KY, Balasubramanyam, V.Morphological variations of the lung fissures and lobes. Indian J Chest Dis Allied Sci 2004;46:179–82.Google ScholarPubMed
Weibel, ER.Morphometry of the Human Lung. Berlin: Springer Verlag, 1963. p. 69.CrossRefGoogle Scholar
Williamson, JP, Armstrong, JJ, McLaughlin, RA.Measuring airway dimensions during bronchoscopy using anatomical optical coherence tomography. Eur Respir J 2010;35:34–41.CrossRefGoogle ScholarPubMed
Kuhn, C.Normal anatomy and histology. In Thurlbeck, WM, Churg, AM, eds. Pathology of the Lung, 2nd ed. New York: Thieme Medical, 1995. pp. 1–36.Google Scholar
Weibel, ER, Sapoval, B, Filoche, M.Design of peripheral airways for efficient gas exchange. Respir Physiol Neurobiol 2005;148:3–21.CrossRefGoogle ScholarPubMed
Heppleston, AG.The pathological anatomy of simple pneumoconiosis in coal workers. J Pathol Bacteriol 1953;66:235–46.CrossRefGoogle ScholarPubMed
Ochs, M, Nyengaard, JR, Jung, A et al. The number of alveoli in the human lung. Am J Respir Crit Care Med 2004;169:120–4.CrossRefGoogle ScholarPubMed
Brusasco, V, Dinh-Xuan, AT.Stereology – a bridge to a better understanding of lung structure and function. Eur Respir J 2010;35:477–8.CrossRefGoogle ScholarPubMed
Weibel, ER, Hsia, CC, Ochs, M.How much is there really? Why stereology is essential in lung morphometry. J Appl Physiol 2006;102:459–67.CrossRefGoogle ScholarPubMed
Miller, WS.The Lung, 2nd ed. Springfield, IL: Charles C Thomas, 1947.Google ScholarPubMed
Verbeken, EK, Cauberghs, M, Van De Woestijne, KP.Membranous bronchioles and connective tissue network of normal and emphysematous lungs. J Appl Physiol 1996;81:2468–80.CrossRefGoogle ScholarPubMed
Aird, WC.Phenotypic heterogeneity of the endothelium: II. Representative vascular beds. Circ Res 2007;100:174–90.CrossRefGoogle ScholarPubMed
Widdicombe, J.The airway vasculature. Exp Physiol 1993;78:433–52.CrossRefGoogle ScholarPubMed
Wagner, EW, Mitzner, W, Brown, RH.Site of functional bronchopulmonary anatomoses in sheep. Anat Rec 1999;254:360–6.3.0.CO;2-4>CrossRefGoogle Scholar
Huang, W, Yen, RT, McLaurine, M, Bledsoe, G.Morphometry of the human pulmonary vasculature. J Appl Physiol 1996;81:2123–33.CrossRefGoogle ScholarPubMed
Riquet, M.Bronchial arteries and lymphatics of the lung. Thorac Surg Clin 2007;17:619–38.CrossRefGoogle ScholarPubMed
Okada, Y, Ito, M, Nagaishi, C.Anatomical study of the pulmonary lymphatics. Lymphology 1979;12:118–24.Google ScholarPubMed
Le Pimpec Barthes, F, Riquet, M, Hartl, D, Hubsch, JP, Hidden, G.Cervical venous anastomoses of pulmonary lymphatic vessels. Surg Radiol Anat 1997;19:53–5.CrossRefGoogle ScholarPubMed
Riquet, M, Le Pimpec Barthes, F, Souilamas, R, Hidden, G.Thoracic duct tributaries from intrathoracic organs. Ann Thorac Surg 2002;73:892–9.CrossRefGoogle ScholarPubMed
Meyer, KK.Direct lymphatic connections from the lower lobes of the lung to the abdomen. J Thorac Surg 1958;35:726–33.Google ScholarPubMed
Yan, G, Zhou, XY, Cai, SJ, Zhang, GH, Peng, JJ, Du, X.Lymphangiogenic and angiogenic microvessel density in human primary sporadic colorectal carcinoma. World J Gastroenterol 2008;14:101–7.CrossRefGoogle ScholarPubMed
Riquet, M, Hidden, G, Debesse, B.Direct lymphatic drainage of lung segments to mediastinal nodes: an anatomic study on 260 adults. J Thorac Cardiovasc Surg 1989;97:623–32.Google ScholarPubMed
Kradin, RL, Spirn, PW, Mark, EJ.Intrapulmonary lymph nodes. Clinical, radiologic, and pathologic features. Chest 1985;87:662–7.CrossRefGoogle ScholarPubMed
Mountain, CF, Dresler, CM.Regional lymph node classification for lung cancer staging. Chest 1997;111:1718–23.CrossRefGoogle ScholarPubMed
van der Velden, VH, Hulsmann, AR.Autonomic innervation of human airways – structure, function, and pathophysiology in asthma. Neuroimmunomodulation 1999;6:145–59.CrossRefGoogle ScholarPubMed
Canning, BJ.Anatomy and neurophysiology of the cough reflex: ACCP evidence-based clinical practice guidelines. Chest 2006;129:33S–47S.CrossRefGoogle ScholarPubMed
Carr, MJ, Undem, BJ.Bronchopulmonary afferent nerves. Respirology 2003;8:291–301.CrossRefGoogle ScholarPubMed
Kubin, L, Alheid, GF, Zuperku, EJ, McCrimmon, DR.Central pathways of pulmonary and lower airway vagal afferents. J Appl Physiol 2006;101:618–27.CrossRefGoogle ScholarPubMed
Canning, BJ.Reflex regulation of airway smooth muscle tone. J Appl Physiol 2006;101:971–85.CrossRefGoogle ScholarPubMed
Barnes, PJ.The third nervous system of the lung: physiology and clinical perspectives. Thorax 1984;39:561–7.CrossRefGoogle ScholarPubMed
Sahn, SA.State of the art. The pleura. Am Rev Respir Dis 1988;138:184–234.CrossRefGoogle ScholarPubMed
Noppen, M, De Waele, M, Li, R et al. Volume and cellular content of normal pleural fluid in humans examined by pleural lavage. Am J Respir Crit Care Med 2000;162:1023–6.CrossRefGoogle ScholarPubMed
Wang, PM, Lai-Fook, SJ.Effects of ventilation on hyaluronan and protein concentration in pleural liquid of anaesthetized and conscious rabbits. Lung 1998;176:309–24.CrossRefGoogle Scholar
Mitchev, K, Dumortier, P, De Vuyst, P.‘Black spots’ and hyaline pleural plaques on the parietal pleura of 150 urban necropsy cases. Am J Surg Pathol 2002;26:1198–206.CrossRefGoogle ScholarPubMed
Boutin, C, Dumortier, P, Rey, F, Viallat, JR, De Vuyst, P.Black spots concentrate oncogenic asbestos fibres in the parietal pleura. Thoracoscopic and mineralogic study. Am J Respir Crit Care Med 1996;153:444–9.CrossRefGoogle ScholarPubMed
Müller, KM, Schmitz, I, Konstantinidis, K.Black spots of the parietal pleura: morphology and formal pathogenesis. Respiration 2002;69:261–7.CrossRefGoogle ScholarPubMed
Franks, TJ, Colby, TV, Travis, WD, et al. Resident cellular components of the human lung: current knowledge and goals for research on cell type and phenotyping and function. Proc Am Thorac Soc 2008;5:763–6.CrossRefGoogle ScholarPubMed
Knight, DA, Holgate, ST.The airway epithelium: structural and functional properties in health and disease. Respirology 2003;8:432–46.CrossRefGoogle ScholarPubMed
Holgate, ST.Epithelial damage and response. Clin Exp Allergy 2000;30:37–41.CrossRefGoogle Scholar
Monkhouse, WS, Whimster, WF.An account of the longitudinal mucosal corrugations of the human tracheo-bronchial tree with observations on those of some animals. J Anat 1976;122:681–95.Google ScholarPubMed
Breeze, RG, Wheeldon, EB.The cells of the pulmonary airways. Am Rev Respir Dis 1977;116:705–77.CrossRefGoogle ScholarPubMed
Sturgess, JM.Mucous secretions of the respiratory tract. Pediatr Clin North Am 1979;26:481–501.CrossRefGoogle ScholarPubMed
Warner, FD, Mitchell, DR, Perkins, CR.Structural conformation of the ciliary ATPase dynein. J Mol Biol 1977;114:367–84.CrossRefGoogle ScholarPubMed
Katial, R, Zheng, W.Allergy and immunology of the aging lung. Clin Chest Med 2007;28:663–72.CrossRefGoogle ScholarPubMed
Thomas, B, Rutman, A, O'Callaghan, C.Disrupted ciliated epithelium shows slower ciliary beat frequency and increased dyskinesia. Eur Respir J 2009;34:401–4.CrossRefGoogle ScholarPubMed
Baldwin, F.Basal cells in human bronchial epithelium. Anat Rec 1994;238:360–7.CrossRefGoogle ScholarPubMed
Hicks, W, Hall, L, Sigurdson, L, et al. Isolation and characterization of basal cells from human upper respiratory epithelium. Exp. Cell Res 1997;237:357–63.CrossRefGoogle ScholarPubMed
Nakajima, M, Kawanami, O, Jin, E, et al. Immunohistochemical and ultrastructural studies of basal cells, Clara cells and bronchiolar cuboidal cells in normal human airways. Pathol Int 1998;48:944–53.CrossRefGoogle ScholarPubMed
Boers, JE, Ambergen, AW, Thunnissen, FBJM.Number and proliferation of basal and parabasal cells in normal human airway epithelium. Am J Respir Crit Care Med 1998;157:2000–6.CrossRefGoogle ScholarPubMed
Hong, KU, Reynolds, SD, Watkins, S, Fuchs, E, Stripp, BR.Basal cells are a multipotent progenitor capable of renewing the bronchial epithelium. Am J Pathol 2004;164:577–88.CrossRefGoogle ScholarPubMed
Inayama, Y, Hook, GE, Brody, AR et al. In vitro and in vivo growth and differentiation of clones of tracheal basal cells. Am J Pathol 1989;134:539–49.Google ScholarPubMed
Randell, SH, Comment, CE, Ramaekers, FC, Nettesheim, P.Properties of rat tracheal epithelial cells separated based on expression of cell surface α-galactosyl end groups. Am J Respir Cell Mol Biol 1991;4:544–54.CrossRefGoogle ScholarPubMed
Evans, MJ, Plopper, CG.The role of basal cells in adhesion of columnar epithelium to airway basement membrane. Am Rev Respir Dis 1988;138:481–3.CrossRefGoogle ScholarPubMed
Evans, MJ, Moller, PC.Biology of airway basal cells. Exp Lung Res 1991;17:513–31.CrossRefGoogle ScholarPubMed
Clara, M.Zur Histobiologie des Bronchialepithels. Z Mikrosk Anat Forsch 1937;4:321–47.Google Scholar
Woywodt, A, Lefrak, S, Matteson, E.Tainted eponyms in medicine: the “Clara” cell joins the list. Eur Respir J 2010;36:706–8.CrossRefGoogle ScholarPubMed
Winkelmann, A, Noack, T.The Clara cell: a “Third Reich eponym”?Eur Respir J 2010;36:722–7.CrossRefGoogle ScholarPubMed
Boers, JE, Ambergen, AW, Thunnissen, FBJM.Number and proliferation of Clara cells in normal human airway epithelium. Am J Respir Crit Care Med 1999;159:1585–91.CrossRefGoogle ScholarPubMed
De Proost, I, Pintelon, I, Brouns, I, et al. Functional live cell imaging of the pulmonary neuroepithelial body microenvironment. Am J Respir Cell Mol Biol 2008;39:180–9.CrossRefGoogle ScholarPubMed
Plopper, CG, Hill, LH, Mariassy, AT.Ultrastructure of the nonciliated bronchiolar epithelial (Clara) cell of mammalian lung. III. A study of man with comparison of 15 mammalian species. Exp Lung Res 1980;1:171–80.CrossRefGoogle Scholar
Barth, PJ, Koch, S, Müller, B, Unterstab, F, von Witchert, P, Moll, R.Proliferation and number of Clara cell 10-kDa protein (CC10) reactive epithelial cells and basal cells in normal, hyperplastic and metaplastic bronchial mucosa. Virchows Arch 2000;437:648–55.CrossRefGoogle ScholarPubMed
Bedetti, CD, Singh, J, Singh, G, Katyal, SL, Wong-Chong, ML.Ultrastructural localization of rat Clara cell 10 KD secretory protein by the immunogold technique using polyclonal and monoclonal antibodies. J Histochem Cytochem 1987;35:789–94.CrossRefGoogle ScholarPubMed
Singh, G, Singh, J, Katyal, SL, et al. Identification, cellular localization, isolation, and characterization of human Clara cell-specific 10 KD protein. J Histochem Cytochem 1988;36:73–80.CrossRefGoogle ScholarPubMed
Shijubo, N, Itoh, Y, Yamaguchi, T, et al. Serum and BAL Clara cell 10 kDa protein (CC10) levels and CC10-positive bronchiolar cells are decreased in smokers. Eur Respir J 1997;10:1108–14.CrossRefGoogle ScholarPubMed
Ryerse, JS, Hoffmann, JW, Mahmoud, S, Nagel, BA, deMello, DE.Immunolocalisation of CC10 in Clara cells in mouse and human lung. Histochem Cell Biol 2001;115:325–32.Google Scholar
Evans, MJ, Shami, SG, Cabral-Anderson, LJ, Dekker, NP.Role of non-ciliated cells in renewal of the bronchial epithelium of rats exposed to NO2. Am J Pathol 1986;123:126–33.Google Scholar
Borthwick, DW, Shahbazian, M, Krantz, QT, Dorin, JR, Randell, SH.Evidence for stem-cell niches in the tracheal epithelium. Am J Respir Cell Mol Biol 2001;24:662–70.CrossRefGoogle ScholarPubMed
Auten, RL, Watkins, RH, Shapiro, DL, Horowitz, S.Surfactant apoprotein-A (SP-A) is synthesized in airway cells. Am J Respir Cell Mol Biol 1990;3:491–6.CrossRefGoogle ScholarPubMed
Reynolds, SD, Malkinson, AM.Clara cell: progenitor for the bronchiolar epithelium. J Biochem Cell Biol 2010;42:1–4.CrossRefGoogle ScholarPubMed
De Water, R, Willems, LN, Van Muijen, GN et al. Ultrastructural localization of bronchial antileukoprotease in central and peripheral human airways by a gold-labeling technique using monoclonal antibodies. Am Rev Respir Dis 1986;133:882–90.Google ScholarPubMed
Singh, G, Katyal, SL.An immunologic study of the secretory products of rat Clara cells. J Histochem Cytochem 1984;32:49–54.CrossRefGoogle ScholarPubMed
Blomberg, A, Mudway, I, Svensson, M, et al. Clara cell protein as a biomarker for ozone-induced lung injury in humans. Eur Respir J 2003;22:883–8.CrossRefGoogle ScholarPubMed
Helleday, R, Segerstedt, B, Forsberg, B, et al. Exploring the time dependence of serum Clara cell protein as a biomarker of pulmonary injury in humans. Chest 2006;130:672–5.CrossRefGoogle ScholarPubMed
Reynolds, SD, Giangreco, A, Power, JH, Stripp, BR.Neuroepithelial bodies of pulmonary airways serve as a reservoir of progenitor cells capable of epithelial regeneration. Am J Pathol 2000;156:269–78.CrossRefGoogle ScholarPubMed
Giangreco, A, Reynolds, SD, Stripp, BR.Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction. Am J Pathol 2002;161:173–82.CrossRefGoogle ScholarPubMed
Hong, KU, Reynolds, SD, Giangreco, A, Hurley, CM, Stripp, BR.Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion. Am J Respir Cell Mol Biol 2001;24:671–81.CrossRefGoogle ScholarPubMed
Stevens, TP, McBride, JT, Peake, JL, Pinkerton, KE, Stripp, BR.Cell proliferation contributes to PNEC hyperplasia after acute airway injury. Am J Physiol 1997;272:L486–93.Google ScholarPubMed
Ayers, MM, Jeffery, PK.Proliferation and differentiation in mammalian airway epithelium. Eur Respir J 1988;1:58–80.Google ScholarPubMed
Rogers, DF.Airway goblet cells: responsive and adaptable front-line defenders. Eur Respir J 1994;7:1690–706.CrossRefGoogle ScholarPubMed
Innes, AL, Woodruff, PG, Ferrando, RE, et al. Epithelial mucin stores are increased in large airways of smokers with airflow obstruction. Chest 2006;130:1102–8.CrossRefGoogle ScholarPubMed
Saetta, M, Turato, G, Baraldo, S, et al. Goblet cell hyperplasia and epithelial inflammation in peripheral airways of smokers with both symptoms of chronic bronchitis and chronic airflow limitation. Am J Respir Crit Care Med 2000;161:1016–21.CrossRefGoogle ScholarPubMed
Lumsden, AB, McLean, A, Lamb, D.Goblet and Clara cells of human distal airways: evidence for smoking induced changes in their numbers. Thorax 1984;39:844–9.CrossRefGoogle ScholarPubMed
Rogers, AV, Dewar, A, Corrin, B, Jeffery, PK.Identification of serous-like cells in the surface epithelium of human bronchioles. Eur Respir J 1993;6:498–504.Google ScholarPubMed
Boujaoude, LC, Bradshaw-Wilder, C, Mao, C, et al. Cystic fibrosis transmembrane regulator regulates uptake of sphingoid base phosphates and lysophosphatidic acid: modulation of cellular activity of sphingosine 1-phosphate. J Biol Chem 2001;276:35258–64.CrossRefGoogle ScholarPubMed
Futerman, AH, Hannun, YA.The complex life of simple sphingolipids. EMBO Rep 2004;5:777–82.CrossRefGoogle ScholarPubMed
Bals, R, Wang, X, Wu, Z et al. Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest 1998;102:874–80.CrossRefGoogle ScholarPubMed
Ganz, T.Antimicrobial polypeptides. J Leukoc Biol 2004;75:34–8.CrossRefGoogle ScholarPubMed
Ballard, ST, Inglis, SK.Liquid secretion properties of airway submucosal glands. J Physiol 2004;556:1–10.CrossRefGoogle ScholarPubMed
Feyrter, F.Über diffuse endokrine epitheliale Organe. Leipzig: J.A. Barth, 1938.Google Scholar
Pearse, AGE.The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J Histochem Cytochem 1969;17:303–13.CrossRefGoogle Scholar
Gosney, JR.Pulmonary Endocrine Pathology: Endocrine Cells and Endocrine Tumours of the Lung. Oxford: Butterworth-Heinemann, 1992.Google Scholar
Van Lommel, A, Bolle, T, Fannes, W, Lauweryns, JM.The pulmonary neuroendocrine system: the past decade. Arch Histol Cytol 1999;62:1–16.CrossRefGoogle ScholarPubMed
Linnoila, RI.Functional facets of the pulmonary neuroendocrine system. Lab Invest 2006;86:425–44.CrossRefGoogle ScholarPubMed
Gosney, JR, Sissons, MCJ, Allibone, RO.Neuroendocrine cell populations in normal human lungs: a quantitative study. Thorax 1988;43:878–82.CrossRefGoogle ScholarPubMed
Gosney, JR.Neuroendocrine cell populations in postnatal human lungs: minimal variation from childhood to old age. Anat Rec 1993;236:177–80.CrossRefGoogle ScholarPubMed
Boers, JE, den Brok, JLM, Koudstaal, J, Arends, JW, Thunnissen, BJM.Number and proliferation of neuroendocrine cells in normal human airway epithelium. Am J Resp Crit Care Med 1996;154:758–63.CrossRefGoogle ScholarPubMed
Lauweryns, JM, Cokelaere, M, Theunynck, P.Neuroepithelial bodies in the respiratory mucosa of various mammals: a light optical, ultrastructural and histochemical investigation. Zellforsch Mikrosk Anat 1972;135:569–92.CrossRefGoogle Scholar
Sorokin, SP, Hoyt, RF.Neuropeithelial bodies and solitary small granule cells. In Massaro, D, ed. Lung Cell Biology. New York: Marcel Dekker, 1989. pp. 191–344.Google Scholar
Weichselbaum, M, Sparrow, MP, Hamilton, EJ, Thompson, PJ, Knight, DA.A confocal microscopic study of solitary pulmonary neuroendocrine cells in human airway epithelium. Respir Res 2005;6:115.CrossRefGoogle ScholarPubMed
Cutz, E, Gillan, JE, Bryan, AC.Neuroendocrine cells in the developing human lung: morphologic and functional considerations. Pediatr Pulmonol 1985;1(3 suppl.):S21–9.Google ScholarPubMed
Gosney, JR.Pulmonary neuroendocrine cell system in pediatric and adult lung disease. Microsc Res Tech 1997;37:107–13.3.0.CO;2-V>CrossRefGoogle ScholarPubMed
Reynolds, SD, Giangreco, A, Power, JHT, Stripp, BR.Neuroepithelial bodies of pulmonary airways serve as a reservoir of progenitor cells capable of epithelial regeneration. Am J Pathol 2000;156:269–78.CrossRefGoogle ScholarPubMed
Wang, D, Yeger, H, Cutz, E.Expression of gastrin-releasing peptide receptor gene in developing lung. Am J Respir Cell Mol Biol 1996;14:409–16.CrossRefGoogle ScholarPubMed
Spindel, ER, Sunday, ME, Hofler, H, Wolfe, HJ, Habener, JF, Chin, WW.Transient elevation of mRNAs encoding gastrin-releasing peptide (GRP), a putative pulmonary growth factor, in human fetal lung. J Clin Invest 1987;80:1172–9.CrossRefGoogle Scholar
Sunday, ME, Hua, J, Dai, HB, Nusrat, A, Torday, JS.Bombesin increases fetal lung growth and maturation in utero and in organ culture. Am J Respir Cell Mol Biol 1990;3:199–205.CrossRefGoogle ScholarPubMed
Siegfried, JM, Guentert, PJ, Gaither, AL.Effects of bombesin and gastrin-releasing peptide on human bronchial epithelial cells from a series of donors: individual variation and modulation by bombesin analogs. Anat Rec 1993:236:241–7.CrossRefGoogle ScholarPubMed
Sunday, ME, Hua, J, Reyes, B, Masui, H, Torday, JS.Anti-bombesin monoclonal antibodies modulate fetal mouse lung growth and maturation in utero and in organ cultures. Anat Rec 1993;236:25–32.CrossRefGoogle ScholarPubMed
Aguayo, SM, Schuyler, WE, Murtagh, JJ, Roman, J.Regulation of lung branching morphogenesis by bombesin-like peptides and neutral endopeptidase. Am J Respir Cell Mol Biol 1994;10:635–42.CrossRefGoogle ScholarPubMed
Li, K, Nagalla, SR, Spindel, ER.A rhesus monkey model to characterize the role of gastrin-releasing peptide (GRP) in lung development. Evidence for stimulation of airway growth. J Clin Invest 1994;94:1605–15.CrossRefGoogle ScholarPubMed
Whitwell, F.Tumourlets of the lung. J Pathol Bacteriol 1955;70:529–41.CrossRefGoogle ScholarPubMed
Tsutsumi, Y, Osamura, RY, Watanabe, K, Yanaihara, N.Immunohistochemical studies on gastrin-releasing peptide and adrenocorticotropic hormone-containing cells in the human lung. Lab Invest 1983;48:623–32.Google ScholarPubMed
Gosney, J, Green, ART, Taylor, W.Appropriate and inappropriate neuroendocrine products in pulmonary tumourlets. Thorax 1990;45:679–83.CrossRefGoogle ScholarPubMed
Gosney, JR, Travis, WD.Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. In Travis, WD, Brambilla, E, Müller-Hermelink, HK, Harris, CC, eds. Pathology and Genetics: Tumours of the Lung, Pleura, Thymus and Heart. Lyon: IARC, 2004. pp. 76–7.Google Scholar
Frohlich, F.Die Helle Zelle der Bronchialschleimhaut und ihre Beziehungen zum Problem der Chemoreceptoren. Frankf Z Pathol 1949;60:517–59.Google Scholar
Polak, J, Becker, KL, Cutz, E, et al. Lung endocrine cell markers, peptides and amines. Anat Rec 1993;236:169–71.CrossRefGoogle ScholarPubMed
Wharton, J, Polak, JM, Bloom, SR, et al. Bombesin-like immunoreactivity in the lung. Nature 1978;273:769–70.CrossRefGoogle ScholarPubMed
Becker, KL, Monaghan, KG, Silva, OL.Immunocytochemical localization of calcitonin in Kulchitsky cells of human lung. Arch Pathol Lab Med 1980;104:196–8.Google ScholarPubMed
Johnson, DE, Wobken, JD.Calcitonin gene-related peptide immunoreactivity in airway epithelial cells of the human fetus and infant. Cell Tissue Res 1987;250:579–83.CrossRefGoogle ScholarPubMed
Lauweryns, JM, de Bock, V, Verhofstad, AAJ, Steinbusch, HWM.Immunohistochemical localization of serotonin in intrapulmonary neuroepithelial bodies. Cell Tissue Res 1982;226:215–23.CrossRefGoogle Scholar
Wick, MR.Immunohistology of neuroendocrine and neuroectodermal tumours. Semin Diagn Pathol 2000;17:194–203.Google Scholar
Scheuermann, DW.Morphology and cytochemistry of the endocrine epithelial system in the lung. Int Rev Cytol 1987;106:35–88.CrossRefGoogle ScholarPubMed
Hofer, D, Drenckhahn, D.Identification of brush cells in the alimentary and respiratory system by antibodies to villin and fimbrin. Histochemistry 1992;98:237–42.CrossRefGoogle ScholarPubMed
Reid, L, Meyrick, B, Antony, VB, Chang, L, Crapo, JD, Reynolds, HY.The mysterious brush cell – a cell in search of a function. Am J Respir Crit Care Med 2005;172:136–9.CrossRefGoogle ScholarPubMed
Chang, LY, Mercer, RR, Crapo, JD.Differential distribution of brush cells in the rat lung. Anat Rec 1986;216:49–54.CrossRefGoogle ScholarPubMed
Sbarbati, A, Osculati, F.A new fate for old cells: brush cells and related elements. J Anat 2005;206:349–58.CrossRefGoogle ScholarPubMed
Sato, A.Tuft cells. Anat Sci Int 2007;82:187–99.CrossRefGoogle ScholarPubMed
Kummer, W, Lips, KS, Pheil, U.The epithelial cholinergic system of the airways. Histochem Cell Biol 2008;130:219–34.CrossRefGoogle ScholarPubMed
McDowell, EM, Combs, JW, Newkirk, C.A quantitative light and electron microscopic study of hamster tracheal epithelium with special attention to so-called ‘intermediate cells.’Exp Lung Res 1983;4:205–26.CrossRefGoogle Scholar
Schittny, JC, Yurchenco, PD.Basement membranes: molecular organization and function in development and disease. Curr Opin Cell Biol 1989;1:983–8.CrossRefGoogle ScholarPubMed
Paulsson, M.Basement membrane proteins – structure, assembly and cellular interactions. Crit Rev Biochem Mol Biol 1992;27:93–127.Google ScholarPubMed
Howat, WJ, Holmes, JA, Holgate, ST, Lackie, PM.Basement membrane pores in human bronchial epithelium – a conduit for infiltrating cells?Am J Pathol 2001;158:673–80.CrossRefGoogle ScholarPubMed
Panettieri, RA, Kotlikoff, MI, Gerthoffer, WT, et al. Airway smooth muscle in bronchial tone, inflammation and remodeling – basic knowledge to clinical relevance. Am J Respir Crit Care Med 2008;177:248–52.CrossRefGoogle ScholarPubMed
Lazaar, AL, Panettieri, RA. Airway smooth muscle as a regulator of immune responses and bronchomotor tone. Clin Chest Med 2006;27:53–69.CrossRefGoogle ScholarPubMed
Mitzner, W.Airway smooth muscle: the appendix of the lung. Am J Respir Crit Care Med 2004;169:787–90.CrossRefGoogle ScholarPubMed
Stephens, NL.Airway smooth muscle. Am Rev Respir Dis 1987;135:960–75.CrossRefGoogle ScholarPubMed
Choi, HK, Finkbeiner, WE, Widdicombe, JH.A comparative study of mammalian tracheal mucous glands. J Anat 2000;197:361–72.CrossRefGoogle ScholarPubMed
Sánchez-Mora, N, Rendón-Henao, J, Monroy, V, Aladro, MH, Álvarez-Fernández, E.Antigenic profile of human bronchial gland. Histol Histopathol 2005;20:865–70.Google ScholarPubMed
Basbaum, CB, Jany, B, Finkbeiner, WE.The serous cell. Annu Rev Physiol 1990;52:97–113.CrossRefGoogle ScholarPubMed
Meyerick, B, Sturgess, JM, Reid, L.A reconstruction of the duct system and secretory tubules of the human bronchial submucosal gland. Thorax 1969;24:729–36.CrossRefGoogle Scholar
Shimura, S, Sasaki, T, Sasaki, H, Takishima, T.Contractility of isolated single submucosal gland from trachea. J Appl Physiol 1986;60:1237–47.CrossRefGoogle ScholarPubMed
Matsuba, K, Takizawa, T, Thurlbeck, WM.Oncocytes in human bronchial glands. Thorax 1972;27:181–4.CrossRefGoogle Scholar
Aubry, MC, Wright, JL, Myers, JL.The pathology of smoking-related lung diseases. Clin Chest Med 2000;21:11–35.CrossRefGoogle ScholarPubMed
Finkbeiner, WE.Physiology and pathology of tracheobronchial glands. Respir Physiol 1999;118:77–83.CrossRefGoogle ScholarPubMed
Wine, JJ, Joo, NS.Submucosal glands and airway defense. Proc Am Thorac Soc 2004;1:47–53.CrossRefGoogle ScholarPubMed
Berman, JS, Beer, DJ, Theodore, AC, Kornfeld, H, Bernard, OJ, Center, DM.Lymphocyte recruitment to the lung. Am Rev Respir Dis 1990;142:238–57.CrossRefGoogle ScholarPubMed
Gould, SJ, Isaacson, PG.Bronchus-associated lymphoid tissue (BALT) in human fetal and infant lung. J Pathol 1993;169:229–34.CrossRefGoogle ScholarPubMed
Tschernig, T, Kleemann, WJ, Pabst, R.Bronchus-associated lymphoid tissue in the lungs of children who died from sudden infant death syndrome and other causes. Thorax 1995;50:658–60.CrossRefGoogle ScholarPubMed
Richmond, I, Pritchard, GE, Ashcroft, T, Avery, A, Corris, PA, Walters, EH.Bronchus associated lymphoid tissue (BALT) in human lung: its distribution in smokers and non-smokers. Thorax 1993;48:1130–4.CrossRefGoogle ScholarPubMed
Sminia, T, van der Brugge-Gamelkoorn, GJ, Jeurissen, SH.Structure and function of bronchus-associated lymphoid tissue (BALT). Crit Rev Immunol 1989;9:119–50.Google Scholar
Bienenstock, J, McDermott, MR.Bronchus- and nasal-associated lymphoid tissues. Immunol Rev 2005;206:22–31.CrossRefGoogle ScholarPubMed
Tschernig, T, Pabst, R.Bronchus associated lymphoid tissue (BALT) is not present in the normal adult lung but in different diseases. Pathobiology 2000;68:1–8.CrossRefGoogle Scholar
Moyron-Quiroz, JE, Rangel-Moreno, J, Kusser, K, et al. Role of inducible bronchus associated lymphoid tissue (iBALT) in respiratory immunity. Nat Med 2004;10:927–34.CrossRefGoogle Scholar
Rangel-Moreno, J, Hartson, L, Navarro, C, Gaxiolla, M, Selman, M, Randall, TD.Inducible bronchus-associated lymphoid tissue (iBALT) in patients with pulmonary complications of rheumatoid arthritis. J Clin Invest 2006;116:3183–94.CrossRefGoogle ScholarPubMed
Colby, TV, Leslie, KO, Yousem, SA.Lungs. In Mills, S, ed. Histology for Pathologists, 3rd ed. Philadelphia, PA: Lippincott, Williams & Wilkins, 2006. pp. 473–504.Google Scholar
Bienenstock, J.Bronchus-associated lymphoid tissue. Int Arch Allergy Appl Immunol 1985;76:62–9.CrossRefGoogle ScholarPubMed
Elliot, JG, Jensen, CM, Mutavdzic, S, Lamb, JP, Carroll, NG, James, AL.Aggregations of lymphoid cells in the airways of nonsmokers, smokers and subjects with asthma. Am J Respir Crit Care Med 2004;169:712–18.CrossRefGoogle ScholarPubMed
Williams, MC.Alveolar type I cells: molecular phenotype and development. Annu Rev Physiol 2003;65:669–95.CrossRefGoogle ScholarPubMed
Evans, MJ, Hackney, JD.Cell proliferation in lungs of mice exposed to elevated concentrations of oxygen. Aerosp Med 1972;43:620–2.Google ScholarPubMed
Danto, SI, Shannon, JM, Borok, Z, Zabski, SM, Crandall, ED.Reversible transdifferentiation of alveolar epithelial cells. Am J Respir Cell Mol Biol 1995;12:497–502.CrossRefGoogle ScholarPubMed
Weibel, ER.The mystery of “non-nucleated plates” in the alveolar epithelium of the lung explained. Acta Anat (Basel) 1971;78:425–43.CrossRefGoogle ScholarPubMed
Chen, Z, Jin, N, Narasaraju, T, et al. Identification of two novel markers for alveolar epithelial type I and II cells. Biochem Biophys Res Commun 2004;319:774–80.CrossRefGoogle ScholarPubMed
Johnson, MD, Bao, HF, Helms, MN.Functional ion channels in pulmonary alveolar type I cells support a role for type I cells in lung ion transport. Proc Natl Acad Sci USA 2006;103:4964–9.CrossRefGoogle ScholarPubMed
Factor, P, Mutlu, GM, Chen, L, et al. Adenosine regulation of alveolar fluid clearance. Proc Natl Acad Sci USA 2007;104:4083–8.CrossRefGoogle ScholarPubMed
Hertzog, EL, Brody, AR, Colby, TV, Mason, R, Williams, MC.Knowns and unknowns of the alveolus. Proc Am Thorac Soc 2008;5:778–82.CrossRefGoogle Scholar
Eaton, DC, Helms, MN, Koval, M, Bao, HF, Jain, L.The contribution of epithelial sodium channels to alveolar function in health and disease. Annu Rev Physiol 2009;71:403–23.CrossRefGoogle ScholarPubMed
Honda, T, Ishida, K, Hayama, M, Kubo, K, Katsuyama, T.Type II pneumocytes are preferentially located along thick elastic fibers forming the framework of human alveoli. Anat Rec 2000;258:34–8.3.0.CO;2-7>CrossRefGoogle ScholarPubMed
Uhal, BD.Cell cycle kinetics in the alveolar epithelium. Am J Physiol 1997;272:L1031–45.Google ScholarPubMed
Mason, RJ.Biology of alveolar type II cells. Respirology 2006;11:S12–15.CrossRefGoogle ScholarPubMed
Verkman, AS, Matthay, MA, Song, Y.Aquaporin water channels and lung physiology. Am J Physiol Lung Cell Mol Physiol 2000;278:L867–79.CrossRefGoogle ScholarPubMed
Venembre, P, Boutten, A, Seta, N, et al. Secretion of alpha 1 antitrypsin by alveolar epithelial cells. FEBS Lett 1994;346:171–4.Google ScholarPubMed
Witherden, IR, Vanden Bon, EJ, Goldstraw, P, et al. Primary human alveolar type II epithelial cell chemokine release: effects of cigarette smoke and neutrophil elastase. Am J Respir Cell Mol Biol 2004;30:500–9.CrossRefGoogle ScholarPubMed
Griese, M.Pulmonary surfactant in health and human lung diseases: state of the art. Eur Respir J 1999;13:1455–76.CrossRefGoogle ScholarPubMed
Katzenstein, AL, Myers, JL.Idiopathic pulmonary fibrosis: clinical relevance of pathological classification. Am J Respir Crit Care Med 1998;157:1301–15.CrossRefGoogle Scholar
Andreeva, AV, Kutuzov, MA, Voyno-Yasenetskaya, TA.Regulation of surfactant secretion in alveolar type II cells. Am J Physiol Lung Cell Mol Physiol 2007;293:L259–71.CrossRefGoogle ScholarPubMed
Wright, JR.The “wisdom” of lung surfactant: balancing host defense and surface tension-reducing functions. Am J Physiol Lung Cell Mol Physiol 2006;291:L847–50.CrossRefGoogle ScholarPubMed
Kishore, U, Greenhough, TJ, Waters, P, et al. Surfactant proteins SP-A and SP-D. Structure, function and receptors. Mol Immunol 2006;43:1293–15.CrossRefGoogle ScholarPubMed
Gardai, SJ, Xiao, YQ, Dickinson, M, et al. By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation. Cell 2003;115:13–23.CrossRefGoogle ScholarPubMed
Wright, JR.Immunoregulatory functions of surfactant proteins. Nat Rev Immunol 2005;5:58–68.CrossRefGoogle ScholarPubMed
Brinker, KG, Martin, E, Borron, P, et al. Surfactant protein D enhances bacterial antigen presentation by bone marrow-derived dendritic cells. Am J Physiol Lung Cell Mol Physiol 2001;281:L1453–63.CrossRefGoogle ScholarPubMed
Brinker, KG, Garner, H, Wright, JR.Surfactant protein A modulates the differentiation of murine bone marrow-derived dendritic cells. Am J Physiol Lung Cell Mol Physiol 2003;284:L232–41.CrossRefGoogle ScholarPubMed
Borron, PJ, Mostaghel, EA, Doyle, C., et al. Pulmonary surfactant proteins A and D directly suppress CD3+/CD4+ cell function: evidence for two shared mechanisms. J Immunol 2002;169:5844–50.CrossRefGoogle Scholar
Chroneos, ZC, Sever-Chroneos, Z, Shepherd, VL.Pulmonary surfactant: an immunological perspective. Cell Physiol Biochem 2010;25:13–26.CrossRefGoogle ScholarPubMed
Rooney, SA, Young, SL, Mendelson, CR.Molecular and cellular processing of lung surfactant. FASEB J 1994;8:957–67.CrossRefGoogle ScholarPubMed
Bates, SR, Dodia, C, Tao, JQ, Fisher, AB.Surfactant protein-a plays an important role in lung surfactant clearance: evidence using the surfactant protein-a gene-targeted mouse. Am J Physiol Lung Cell Mol Physiol 2008;294:L325–33.CrossRefGoogle ScholarPubMed
Ikegami, M, Grant, S, Korfhagen, T, Scheule, RK, Whitsett, JA.Surfactant protein-D regulates the postnatal maturation of pulmonary surfactant lipid pool sizes. J Appl. Physiol 2009;106:1545–52.CrossRefGoogle ScholarPubMed
Bates, SR.P63 (CKAP4) as an SP-A receptor: implications for surfactant turnover. Cell Physiol Biochem 2010;25:41–54.CrossRefGoogle ScholarPubMed
Pastva, AM, Wright, JR, Williams, KL.Immunomodulatory roles of Surfactant Proteins A and D. Implications for lung disease. Proc Am Thorac Soc 2007;4:252–7.CrossRefGoogle Scholar
Kawakami, M, Takizawa, T.Distribution of pores within alveoli in the human lung. J Appl Physiol 1987;63:1866–70.CrossRefGoogle ScholarPubMed
Lambert, MW.Accessory bronchioalveolar communications. J Pathol Bacteriol 1955;70:311–14.CrossRefGoogle Scholar
Delaunois, L.Anatomy and physiology of collateral respiratory pathways. Eur Respir J 1989;2:893–904.Google ScholarPubMed
Starcher, BC.Elastin and the lung. Thorax 1986;41:577–85.CrossRefGoogle ScholarPubMed
Pelosi, P, Rocco, P, Negrini, D, Passi, A.The extracellular matrix of the lung and its role in edema formation. An Acad Bras Cienc 2007;79:285–97.CrossRefGoogle ScholarPubMed
Low, FN.Extracellular components of the pulmonary alveolar wall. Arch Inter Med 1971;127:847–52.CrossRefGoogle ScholarPubMed
Sirianni, FE, Chu, FSF, Walker, DC.Human alveolar wall fibroblasts directly link epithelial type 2 cells to capillary endothelium. Am J Respir Crit Care Med 2003;168:1532–7.CrossRefGoogle ScholarPubMed
Negrini, D, Passi, A.Interstitial matrix and transendothelial fluxes in normal lung. Respir Physiol Neurobiol 2007;159:301–10.CrossRefGoogle ScholarPubMed
Dörger, M, Krombach, F.Interaction of alveolar macrophages with inhaled mineral particulates. J Aerosol Med 2000;13:369–80.CrossRefGoogle ScholarPubMed
Wu, HM, Jin, M, Marsh, CB.Toward functional proteomics of alveolar macrophages. Am J Physiol Lung Cell Mol Physiol 2005;288:L585–95.CrossRefGoogle ScholarPubMed
Shapiro, SD, Senior, RM.Matrix metalloproteinases, matrix degradation and more. Am J Respir Cell Mol Biol 1999;20:1100–2.CrossRefGoogle ScholarPubMed
Rubins, JB.Alveolar macrophages: wielding the double-edged sword of inflammation. Am J Respir Crit Care Med 2003;167:103–4.CrossRefGoogle ScholarPubMed
Fox, B, Bull, TB, Guz, A.Mast cells in the human alveolar wall: An electron microscopic study. J Clin Pathol 1981;34:1333–42.CrossRefGoogle Scholar
Heard, BE, Nunn, AJ, Kay, AB.Mast cells in human lungs. J Pathol 1989;157:59–63.CrossRefGoogle ScholarPubMed
Carroll, NG, Mutavdzic, S, James, AL.Distribution and degranulation of airway mast cells in normal and asthmatic subjects. Eur Respir J 2002;19:879–85.CrossRefGoogle ScholarPubMed
Brightling, CE, Bradding, P.The re-emergence of the mast cell as a pivotal cell in asthma pathogenesis. Curr Allergy Asthma Rep 2005;5:130–5.CrossRefGoogle ScholarPubMed
Vermaelen, K, Pauwels, R.Pulmonary dendritic cells. Am J Respir Crit Care Med 2005;172:530–51.CrossRefGoogle ScholarPubMed
Kheradmand, F, Shan, M, Corry, DB.Smoking gun – mature dendritic cells in human lung provide clues to chronic obstructive pulmonary disease. Am J Resp Crit Care Med 2009;180:1166–7.CrossRefGoogle ScholarPubMed
Freeman, CM, Martinez, FJ, Han, MK, et al. Lung dendritic cell expression of maturation molecules increases with worsening chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2009;180:1179–88.CrossRefGoogle ScholarPubMed
Steinman, RM, Banchereau, J.Taking dendritic cells into medicine. Nature 2007;449:419–26.CrossRefGoogle ScholarPubMed
Lambrecht, BN, Hammad, H.Taking our breath away: dendritic cells in the pathogenesis of asthma. Nat Rev Immunol 2003;3:994–1003.CrossRefGoogle Scholar
Demedts, IK, Brusselle, GG, Vermaelen, KY, Pauwels, RA.Identification and characterization of human pulmonary dendritic cells. Am J Respir Cell Mol Biol 2005;32:177–84.CrossRefGoogle ScholarPubMed
Van Pottelberge, GR, Bracke, KR, Van der Broeck, S, et al. Plasmacytoid dendritic cells in pulmonary lymphoid follicles of patients with COPD. Eur Respir J 2010;36:781–91.CrossRefGoogle ScholarPubMed
Schettini, J, Mukherjee, P.Physiological role of plasmacytoid dendritic cells and their potential use in cancer immunity. Clin Dev Immunol 2008;2008:106321.CrossRefGoogle ScholarPubMed
Demedts, IK, Bracke, KR, Maes, T, et al. Different roles for human lung dendritic cell subsets in pulmonary immune defense mechanisms. Am J Respir Cell Mol Biol 2006;35:387–93CrossRefGoogle ScholarPubMed
Ito, T, Yang, M, Wang, YH, et al. Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand. J Exp Med 2007;204:105–15.CrossRefGoogle Scholar
Mahnke, K, Guo, M, Lee, S, et al. The dendritic cell receptor for endocytosis, DEC-205, can recycle and enhance antigen presentation via major histocompatibility complex, class II-positive lysosomal compartments. J Cell Biol 2000;151:673–84.CrossRefGoogle ScholarPubMed
Sharma, GK, Talbot, IC.Pulmonary megakaryocytes: “missing link” between cardiovascular and respiratory disease?J Clin Pathol 1986;39:969–76.CrossRefGoogle ScholarPubMed
Kasper, M.Phenotypic characterization of pulmonary arteries in normal and diseased lung. Chest 2005;128:547S–52S.CrossRefGoogle ScholarPubMed
Harris, P, Heath, D.The Human Pulmonary Circulation – its Form and Function in Health and Disease, 3rd edn. Edinburgh: Churchill Livingstone, 1986.Google Scholar
Leslie, KO, Wick, M.Practical Pulmonary Pathology: A Diagnostic Approach. Edinburgh: Churchill Livingstone, 2004.Google Scholar
Stenmark, KR, Davie, N, Frid, M, Gerasimovskaya, E, Das, M.Role of the adventitia in pulmonary vascular remodeling. Physiology 2006:21:134–45.CrossRefGoogle ScholarPubMed
Hu, Y, Zhang, Z, Torsney, E, et al. Abundant progenitor cells in the adventitia contribute to atherosclerosis of vein grafts in ApoE-deficient mice. J Clin Invest 2004;113:1258–65.CrossRefGoogle ScholarPubMed
Torsney, E, Xu, Q.Adventitial progenitor cells contribute to arteriosclerosis. Trends Cardiovasc Med 2005;15:64–8.CrossRefGoogle ScholarPubMed
Pries, AR, Kuebler, WM.Normal endothelium. Handb Exp Pharmacol 2006;176:1–40.Google Scholar
Wagenvoort, CA, Wagenvoort, N.Arterial anastomoses, bronchopulmonary arteries and pulmobronchial arteries in perinatal lungs. Lab Invest 1967;16:13–24.Google ScholarPubMed
Butnor, KJ, Cooper, K.Visceral pleural invasion in lung cancer: recognising histologic parameters that impact staging and prognosis. Adv Anat Pathol 2005;12:1–6.CrossRefGoogle Scholar
Flieder, DB.Commonly encountered difficulties in pathologic staging of lung cancer. Arch Pathol Lab Med 2007;131:1016–26.Google ScholarPubMed
Mutsaers, SE.Mesothelial cells: their structure, function and role in serosal repair. Respirology 2002;7:171–91.CrossRefGoogle ScholarPubMed
Mutsaers, SE.The mesothelial cell. Int J Biochem Cell Biol 2004;36:9–16.CrossRefGoogle ScholarPubMed
Michailova, KN, Usunoff, KG.The “milky spots” of the peritoneum and pleura: structure, development and pathology. Biomed Rev 2004;15:47–66.CrossRefGoogle Scholar
Leblond, CP, Inoue, S.Structure, composition and assembly of basement membrane. Am J Anat 1989;185:367–90.CrossRefGoogle ScholarPubMed
Kampmeier, OF.Concerning certain mesothelial thickenings and vascular plexus of the mediastinal pleura associated with histiocyte and fat cell production in the human newborn. Anat Rec 1928;39:201–8.CrossRefGoogle Scholar
Wang, QX, Ohtani, O, Saitoh, M, Ohtani, Y.Distribution and ultrastructure of the stomata connecting the pleural cavity with lymphatics in the rat costal pleura. Acta Anat (Basel) 1997;158:255–65.CrossRefGoogle ScholarPubMed
Li, J.Ultrastructural study on the pleural stomata in human. Func Dev Morphol 1993;3:277–80.Google ScholarPubMed
Li, J, Zhao, Z, Zhou, J, Yu, S.A study of the three dimensional organization of the human diaphragmatic lymphatic lacunae and lymphatic drainage units. Ann Anat 1996;178:537–44.CrossRefGoogle ScholarPubMed
Michailova, KN.Electron microscopic observation on the visceral and parietal rat's pleura after contralateral pneumonectomy. Eur J Morphol 2001;39:47–56.CrossRefGoogle Scholar
Kirkwood, TB, Austad, SN.Why do we age?Nature 2000;408:223–38.CrossRefGoogle ScholarPubMed
Papazoglu, C, Mills, AA.p53: at the crossroad between cancer and ageing. J Pathol 2007;211:124–33.CrossRefGoogle ScholarPubMed
Shay, JW, Wright, WE.Hallmarks of telomeres in ageing research. J Pathol 2007;211:114–23.CrossRefGoogle ScholarPubMed
Sharma, G, Goodwin, J.Effect of aging on respiratory system physiology and function. Clin Interv Aging 2006;1:253–60.CrossRefGoogle Scholar
Meyer, KC.Ageing. Proc Am Thorac Soc 2005;2:433–9.CrossRefGoogle Scholar
Gillooly, M, Lamb, D.Microscopic emphysema in relation to age and smoking habit. Thorax 1993;48:491–5.CrossRefGoogle ScholarPubMed
Heath, D.Structural changes in the pulmonary vasculature associated with aging. In Cander, L, Moyer, JH, eds. Aging of the Lung. New York: Grune & Stratton, 1965.Google Scholar
Brenner, O.Pathology of the vessels of the pulmonary circulation. Arch Intern Med 1935;56:211–37.CrossRefGoogle Scholar
Kunze, WP.Senile pulmonary amyloidosis. Pathol Res Pract 1979;164:413–22.CrossRefGoogle ScholarPubMed
Westermark, P, Bergstrom, J, Solomon, A, Murphy, C, Sletten, K.Transthyretin-derived senile systemic amyloidosis: clinicopathologic and structural considerations. Amyloid 2003;10 Suppl 1:48–54.Google Scholar
Tolep, K, Higgins, N, Muza, S, et al. Comparison of diaphragm strength between healthy adult elderly and young men. Am J Crit Care Med 1995;152:677–82.CrossRefGoogle ScholarPubMed
Ho, JC, Chan, KN, Hu, WH, et al. The effect of aging on nasal mucociliary clearance, beat frequency, and ultrastructure of respiratory cilia. Am J Respir Crit Care Med 2001;163:983–8.CrossRefGoogle ScholarPubMed
Meyer, KC, Ershler, W, Rosenthal, NS, et al. Immune dysregulation in the aging human lung. Am J Respir Crit Care Med 1996;153:1072–9.CrossRefGoogle ScholarPubMed
Kikuchi, R, Watabe, N, Konno, T, et al. High incidence of silent aspiration in elderly patients with community acquired pneumonia. Am J Respir Crit Care Med 1994;150:251–3.CrossRefGoogle ScholarPubMed
Matsuse, T, Oka, T, Kida, K, Fukuchi, Y.Importance of diffuse aspiration bronchiolitis caused by chronic occult aspiration in the elderly. Chest 1996;110:1289–93.CrossRefGoogle ScholarPubMed
Palmer, LB, Albulak, K, Fields, S, et al. Oral clearance and pathogenic oropharyngeal colonization in the elderly. Am J Respir Crit Care Med 2001;164:464–8.CrossRefGoogle ScholarPubMed

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