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Pathological Alternations of Mediastinal Fat-Associated Lymphoid Cluster and Lung in a Streptozotocin-Induced Diabetic Mouse Model

Published online by Cambridge University Press:  21 December 2020

Yaser H.A. Elewa*
Affiliation:
Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita18-Nishi 9, Kita-Ku, Sapporo, Hokkaido060-0818, Japan
Osamu Ichii
Affiliation:
Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita18-Nishi 9, Kita-Ku, Sapporo, Hokkaido060-0818, Japan Laboratory of Agrobiomedical Science, Faculty of Agriculture, Hokkaido University, Sapporo, Japan
Teppei Nakamura
Affiliation:
Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita18-Nishi 9, Kita-Ku, Sapporo, Hokkaido060-0818, Japan Department of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories, Chitose, Japan
Yasuhiro Kon
Affiliation:
Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita18-Nishi 9, Kita-Ku, Sapporo, Hokkaido060-0818, Japan
*
*Author for correspondence: Yaser Elewa, E-mail: y-elewa@vetmed.hokudai.ac.jp, yaserelewa@zu.edu.eg
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Abstract

Diabetes is a devastating global health problem and is considered a predisposing factor for lung injury progression. Furthermore, previous reports of the authors revealed the role of mediastinal fat-associated lymphoid clusters (MFALCs) in advancing respiratory diseases. However, no reports concerning the role of MFALCs on the development of lung injury in diabetes have been published. Therefore, this study aimed to examine the correlations between diabetes and the development of MFALCs and the progression of lung injury in a streptozotocin-induced diabetic mouse model. Furthermore, immunohistochemical analysis for immune cells (CD3+ T-lymphocytes, B220+ B-lymphocytes, Iba1+ macrophages, and Gr1+ granulocytes), vessels markers (CD31+ endothelial cells and LYVE-1+ lymphatic vessels “LVs”), and inflammatory markers (TNF-α and IL-5) was performed. In comparison to the control group, the diabetic group showed lung injury development with a significant increase in MFALC size, immune cells, LVs, and inflammatory marker, and a considerable decrease of CD31+ endothelial cells in both lung and MFALCs was observed. Furthermore, the blood glucose level showed significant positive correlations with MFALCs size, lung injury, immune cells, inflammatory markers, and LYVE-1+ LVs in lungs and MFALCs. Thus, we suggest that the development of MFALCs and LVs could contribute to lung injury progression in diabetic conditions.

Type
Biological Applications
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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References

Aggarwal, BB (2003). Signalling pathways of the TNF superfamily: A double-edged sword. Nat Rev Immunol 3(9), 745756.CrossRefGoogle ScholarPubMed
Aggarwal, BB, Gupta, SC & Kim, JH (2012). Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey. Blood 119(3), 651665.CrossRefGoogle ScholarPubMed
Akbarzadeh, A, Norouzian, D, Mehrabi, M, Jamshidi, S, Farhangi, A, Verdi, AA, Mofidian, S & Rad, BL (2007). Induction of diabetes by streptozotocin in rats. Indian J Clin Biochem 22(2), 6064.CrossRefGoogle ScholarPubMed
Ashcroft, T, Simpson, JM & Timbrell, V (1988). Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol 41(4), 467470.CrossRefGoogle ScholarPubMed
Bajpai, S (2018). Chapter 8 – Biological importance of Aloe vera and its active constituents. In Synthesis of Medicinal Agents From Plants, Tewari, A & Tiwari, S (Eds.), pp. 177203. Amity School of Applied Sciences, Amity University, Lucknow, India: Elsevier.CrossRefGoogle Scholar
Benezech, C, Luu, NT, Walker, JA, Kruglov, AA, Loo, Y, Nakamura, K, Zhang, Y, Nayar, S, Jones, LH, Flores-Langarica, A, McIntosh, A, Marshall, J, Barone, F, Besra, G, Miles, K, Allen, JE, Gray, M, Kollias, G, Cunningham, AF, Withers, DR, Toellner, KM, Jones, ND, Veldhoen, M, Nedospasov, SA, McKenzie, ANJ & Caamano, JH (2015). Inflammation-induced formation of fat-associated lymphoid clusters. Nat Immunol 16(8), 819.CrossRefGoogle ScholarPubMed
Boonyarattanasoonthorn, T, Elewa, YHA, Tag-El-Din-Hassan, HT, Morimatsu, M & Agui, T (2019). Profiling of cellular immune responses to Mycoplasma pulmonis infection in C57BL/6 and DBA/2 mice. Infect. Genet Evol 73, 5565.CrossRefGoogle ScholarPubMed
Buscher, K, Wang, H, Zhang, X, Striewski, P, Wirth, B, Saggu, G, Lütke-Enking, S, Mayadas, TN, Ley, K, Sorokin, L & Song, J (2016). Protection from septic peritonitis by rapid neutrophil recruitment through omental high endothelial venules. Nat Commun 7, 10828.CrossRefGoogle ScholarPubMed
De Santi, F, Zoppini, G, Locatelli, F, Finocchio, E, Cappa, V, Dauriz, M & Verlato, G (2017). Type 2 diabetes is associated with an increased prevalence of respiratory symptoms as compared to the general population. BMC Pulm Med 17(1), 101.CrossRefGoogle ScholarPubMed
Ehrlich, SF, Quesenberry, CP Jr., Van Den Eeden, SK, Shan, J & Ferrara, A (2010). Patients diagnosed with diabetes are at increased risk for asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and pneumonia but not lung cancer. Diabetes Care 33(1), 5560.CrossRefGoogle Scholar
Eleazu, CO, Eleazu, KC, Chukwuma, S & Essien, UN (2013). Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans. J Diabetes Metab Disord 12(1), 60.CrossRefGoogle ScholarPubMed
Elewa, YH, Ichii, O & Kon, Y (2016). Comparative analysis of mediastinal fat-associated lymphoid cluster development and lung cellular infiltration in murine autoimmune disease models and the corresponding normal control strains. Immunology 147(1), 3040.CrossRefGoogle ScholarPubMed
Elewa, YHA, Ichii, O & Kon, Y (2017). Sex-related differences in autoimmune-induced lung lesions in MRL/MpJ-faslpr mice are mediated by the development of mediastinal fat-associated lymphoid clusters. Autoimmunity 50(5), 306316.CrossRefGoogle ScholarPubMed
Elewa, YHA, Ichii, O, Otsuka, S, Hashimoto, Y & Kon, Y (2014). Characterization of mouse mediastinal fat-associated lymphoid clusters. Cell Tissue Res 357(3), 731741.CrossRefGoogle ScholarPubMed
Elewa, YHA, Ichii, O, Takada, K, Nakamura, T, Masum, MA & Kon, Y (2018). Histopathological correlations between mediastinal fat-associated lymphoid clusters and the development of lung inflammation and fibrosis following bleomycin administration in mice. Front Immunol 9, 271.CrossRefGoogle ScholarPubMed
Erickson, LD, Foy, TM & Waldschmidt, TJ (2001). Murine B1 B cells require IL-5 for optimal T cell-dependent activation. J Immunol 166(3), 15311539.CrossRefGoogle ScholarPubMed
Fong, DS, Aiello, L, Gardner, TW, King, GL, Blankenship, G, Cavallerano, JD, Ferris, FL & Klein, R (2004). Retinopathy in diabetes. Diabetes Care 27(suppl 1), s84s87.CrossRefGoogle ScholarPubMed
Girard, JP & Springer, TA (1995). High endothelial venules (HEVs): Specialized endothelium for lymphocyte migration. Immunol Today 16(9), 449457.CrossRefGoogle ScholarPubMed
Goud, BJ, Dwarakanath, V & Chikka, BK (2015). Streptozotocin – A diabetogenic agent in animal models. Int J Pharm Pharm Res 3(1), 253269.Google Scholar
Honiden, S & Gong, MN (2009). Diabetes, insulin, and development of acute lung injury. Crit Care Med 37(8), 24552464.CrossRefGoogle ScholarPubMed
Ichii, O, Otsuka, S, Sasaki, N, Yabuki, A, Ohta, H, Takiguchi, M, Hashimoto, Y, Endoh, D & Kon, Y (2010). Local overexpression of interleukin-1 family, member 6 relates to the development of tubulointerstitial lesions. Lab Invest 90(3), 459475.CrossRefGoogle ScholarPubMed
Kario, K, Ishikawa, J, Hoshide, S, Matsui, Y, Morinari, M, Eguchi, K, Ishikawa, S & Shimada, KJH (2005). Diabetic brain damage in hypertension: Role of renin-angiotensin system. Hypertension 45(5), 887893.CrossRefGoogle ScholarPubMed
Kolluru, GK, Bir, SC & Kevil, CG (2012). Endothelial dysfunction and diabetes: Effects on angiogenesis, vascular remodeling, and wound healing. Int J Vas Medicine 2012, 918267.Google ScholarPubMed
Malaviya, R, Laskin, JD & Laskin, DL (2017). Anti-TNFα therapy in inflammatory lung diseases. Pharmacol Ther 180, 9098.CrossRefGoogle ScholarPubMed
Martin, A, Komada, MR & Sane, DC (2003). Abnormal angiogenesis in diabetes mellitus. Med Res Rev 23(2), 117145.CrossRefGoogle ScholarPubMed
Moro, K, Yamada, T, Tanabe, M, Takeuchi, T, Ikawa, T, Kawamoto, H, Furusawa, J, Ohtani, M, Fujii, H & Koyasu, S (2010). Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature 463(7280), 540544.CrossRefGoogle Scholar
Mukhopadhyay, S, Hoidal, JR & Mukherjee, TK (2006). Role of TNFalpha in pulmonary pathophysiology. Respir Res 7(1), 125.CrossRefGoogle ScholarPubMed
Pitocco, D, Fuso, L, Conte, EG, Zaccardi, F, Condoluci, C, Scavone, G, Incalzi, RA & Ghirlanda, G (2012). The diabetic lung – A new target organ? Rev Diabet Stud 9(1), 2335.CrossRefGoogle Scholar
Rangel-Moreno, J, Moyron-Quiroz, JE, Carragher, DM, Kusser, K, Hartson, L, Moquin, A & Randall, TD (2009). Omental milky spots develop in the absence of lymphoid tissue-inducer cells and support B and T cell responses to peritoneal antigens. Immunity 30(5), 731743.CrossRefGoogle Scholar
Reed, HO, Wang, L, Sonett, J, Chen, M, Yang, J, Li, L, Aradi, P, Jakus, Z, D'Armiento, J, Hancock, WW & Kahn, ML (2019). Lymphatic impairment leads to pulmonary tertiary lymphoid organ formation and alveolar damage. J Clin Invest 129(6), 25142526.CrossRefGoogle ScholarPubMed
Samarghandian, S, Afshari, R & Sadati, A (2014). Evaluation of lung and bronchoalveolar lavage fluid oxidative stress indices for assessing the preventing effects of safranal on respiratory distress in diabetic rats. Sci World J.2014, 251378.CrossRefGoogle ScholarPubMed
Sandler, M (1990). Is the lung a ‘target organ’ in diabetes mellitus? Arch Inter Med 150(7), 13851388.CrossRefGoogle Scholar
Scano, G, Seghieri, G, Mancini, M, Filippelli, M, Duranti, R, Fabbri, A, Innocenti, F, Iandelli, I & Misuri, G (1999). Dyspnoea, peripheral airway involvement and respiratory muscle effort in patients with type I diabetes mellitus under good metabolic control. Clin Sci (Lond) 96(5), 499506.CrossRefGoogle ScholarPubMed
Sonoda, E, Matsumoto, R, Hitoshi, Y, Ishii, T, Sugimoto, M, Araki, S, Tominaga, A, Yamaguchi, N & Takatsu, K (1989). Transforming growth factor beta induces IgA production and acts additively with interleukin 5 for IgA production. J Exp Med 170(4), 14151420.CrossRefGoogle ScholarPubMed
Suzuki, J, Hamada, E, Shodai, T, Kamoshida, G, Kudo, S, Itoh, S, Koike, J, Nagata, K, Irimura, T & Tsuji, T (2013). Cytokine secretion from human monocytes potentiated by P-selectin-mediated cell adhesion. Int Arch Allergy Appl Immunol 160(2), 152160.CrossRefGoogle ScholarPubMed
Talakatta, G, Sarikhani, M, Muhamed, J, Dhanya, K, Somashekar, BS, Mahesh, PA, Sundaresan, N & Ravindra, PV (2018). Diabetes induces fibrotic changes in the lung through the activation of TGF-β signaling pathways. Sci Rep 8(1), 11920.CrossRefGoogle ScholarPubMed
Tamura, J, Konno, A, Hashimoto, Y & Kon, Y (2005). Upregulation of renal renin-angiotensin system in mouse diabetic nephropathy. Jpn J Vet Res 53(1–2), 1326.Google ScholarPubMed
Tervaert, TWC, Mooyaart, AL, Amann, K, Cohen, AH, Cook, HT, Drachenberg, CB, Ferrario, F, Fogo, AB, Haas, M, de Heer, E, Joh, K, Noël, LH, Radhakrishnan, J, Seshan, SV, Bajema, IM & Bruijn, JA (2010). Pathologic classification of diabetic nephropathy. J Am Soc Nephrol 21(4), 556563.CrossRefGoogle ScholarPubMed
Tesfaye, S, Chaturvedi, N, Eaton, SE, Ward, JD, Manes, C, Ionescu-Tirgoviste, C, Witte, DR & Fuller, JH (2005). Vascular risk factors and diabetic neuropathy. N Engl J Med 352(4), 341350.CrossRefGoogle ScholarPubMed
van Lunteren, E, Moyer, M & Spiegler, S (2014). Alterations in lung gene expression in streptozotocin-induced diabetic rats. BMC Endocr Disord 14(1), 5.CrossRefGoogle ScholarPubMed
Ventura-Sobrevilla, J, Boone-Villa, VD, Aguilar, CN, Román-Ramos, R, Vega-Avila, E, Campos-Sepúlveda, E & Alarcón-Aguilar, F (2011). Effect of varying dose and administration of streptozotocin on blood sugar in male CD1 mice. Proc West Pharmacol Soc 54, 59.Google ScholarPubMed
Xu, L, Kanasaki, K, Kitada, M & Koya, D (2012). Diabetic angiopathy and angiogenic defects. Fibrogenesis Tissue Repair 5(1), 1313.CrossRefGoogle ScholarPubMed
Zheng, H, Wu, J, Jin, Z & Yan, L-J (2017). Potential biochemical mechanisms of lung injury in diabetes. Aging Dis 8(1), 716.CrossRefGoogle ScholarPubMed
Zou, X-Z, Gong, Z-C, Liu, T, He, F, Zhu, T-T, Li, D, Zhang, W-F, Jiang, J-L & Hu, C-P (2017). Involvement of epithelial-mesenchymal transition afforded by activation of LOX-1/TGF-β1/KLF6 signaling pathway in diabetic pulmonary fibrosis. Pulm Pharmacol Ther 44, 7077.CrossRefGoogle ScholarPubMed