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Effect of aprotinin on in vitro cerebral endothelial ICAM-1 expression induced by astrocyte-conditioned medium

Published online by Cambridge University Press:  29 April 2005

D. Harmon ,
K. Ghori ,
W. Lan  and
G. Shorten
D. Harmon
Affiliation:
Walton Centre for Neurology and Neurosurgery, Liverpool, UK
K. Ghori
Affiliation:
Cork University Hospital and University College Cork, Department of Anaesthesia and Intensive Care Medicine, Cork, Ireland
W. Lan
Affiliation:
Cork University Hospital and University College Cork, Department of Surgery, Cork, Ireland
G. Shorten
Affiliation:
Cork University Hospital and University College Cork, Department of Anaesthesia and Intensive Care Medicine, Cork, Ireland
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Abstract

Summary

Background and objective: Aprotinin administration may decrease the incidence of stroke associated with coronary artery bypass surgery by an unknown mechanism. Astrocytes exposed to hypoxia produce proinflammatory cytokines and upregulate intercellular adhesion molecule (ICAM)-1 on cerebral endothelium. This study investigated the effects of aprotinin on cerebral endothelial activation by hypoxic astrocytes in vitro.

Methods: Mouse astrocytes were exposed to hypoxia in an anaerobic chamber for 4 h followed by reoxygenation for 24 h. Astrocyte-conditioned medium (ACM) collected from mouse astrocytes subjected to hypoxia/reoxygenation (HR) or normoxia were applied to mouse cerebral endothelial cell (MCEC) cultures for 4 and 24 h in normoxia. Endothelial cells were preincubated for 1 h with aprotinin (1600 KIU mL−1) prior to exposure to ACM. Flow cytometry was used to estimate endothelial ICAM-1 expression. Interleukin (IL)-1β space concentrations in ACM were estimated with enzyme-linked immunosorbent assay (ELISA). Repeated comparisons were made using analysis of variance (ANOVA) and post hoc Tukey test as appropriate. P < 0.05 was considered significant. Data is presented as mean (standard deviation, SD).

Results: MCEC ICAM-1 expression was greater after 24 h exposure to HR-ACM compared to normoxic-ACM (mean channel flouresence (MCF) 107.5 (4.5) vs. 74.3 (4.5), respectively, P < 0.001). ICAM-1 expression was decreased by aprotinin preincubation compared to control (MCF 91.0 (1.1) vs. 107.5 (2.1), P = 0.006). Supernatant IL-1β concentrations in astrocytes exposed to HR were greater than those exposed to normoxia (7.1 (0.2) vs. 4.1 (0.2), P = 0.01).

Conclusions: This may be a neuroprotective mechanism associated with aprotinin administration.

Keywords

INFLAMMATIONCELL ADHESION MOLECULES, intercellular adhesion molecule-1PROTEINS, aprotininCENTRAL NERVOUS SYSTEM, neuroprotective agentshypoxia–ischaemia, brain
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 22 , Issue 4 , April 2005 , pp. 277 - 282
Copyright
2005 European Society of Anaesthesiology

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References

Alderman EL, Levy JH, Rich JB, et al. Analyses of coronary graft patency after aprotinin use: results from the International Multicenter Aprotinin Graft Patency Experience (IMAGE) trial. J Thorac Cardiovasc Surg 1998; 116: 716–730.Google Scholar
Murkin JM. Attenuation of neurologic injury during cardiac surgery. Ann Thorac Surg 2001; 72: S1838–S1844.Google Scholar
Barone FC, Feuerstein GZ. Inflammatory mediators and stroke: new opportunities for novel therapeutics. J Cereb Blood Flow Metab 1999; 19: 819–834.Google Scholar
Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 1999; 22: 391–397.Google Scholar
Barone FC, Schmidt DB, Hillegass LM, et al. Reperfusion increases neutrophils and leukotriene B4 receptor binding in rat focal ischemia. Stroke 1992; 23: 1337–1347.Google Scholar
Clark RK, Lee EV, White RF, Jonak ZL, Feuerstein GZ, Barone FC. Reperfusion following focal stroke hastens inflammation and resolution of the ischemic injured tissue. Brain Res Bull 1994; 35: 387–392.Google Scholar
Chopp M, Zhang RL, Chen H, Li Y, Jiang N, Rusche JR. Postischemic administration of an anti-Mac-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in rats. Stroke 1994; 25: 869–876.Google Scholar
Wang X, Feuerstein GZ. Induced expression of adhesion molecules following focal brain ischemia. J Neurotrauma 1995; 12: 825–832.Google Scholar
Stanimirovic D, Satoh K. Inflammatory mediators of cerebral endothelium: a role in ischemic brain inflammation. Brain Pathol 2000; 10: 113–126.Google Scholar
Nagy Z, Kolev K, Csonka E, Pek M, Machovich R. Contraction of human brain endothelial cells induced by thrombogenic and fibrinolytic factors. An in vitro cell culture model. Stroke 1995; 26: 265–270.Google Scholar
Joo J. Endothelial cells of the brain and other organ systems: some similarities and differences. Prog Neurobiol 1996; 48: 255–273.Google Scholar
Zhang W, Smith C, Howlett C, Stanimirovic D. Inflammatory activation of human brain endothelial cells by hypoxic astrocytes in vitro is mediated by IL-1 beta. J Cereb Blood Flow Metab 2000; 20: 967–978.Google Scholar
Tan KH, Dobbie MS, Felix RA, Barrand MA, Hurst RD. A comparison of the induction of immortalized endothelial cell impermeability by astrocytes. NeuroReport 2001; 12: 1329–1334.Google Scholar
Yoder EJ. Modifications in astrocyte morphology and calcium signalling induced by a brain capillary endothelial cell line. Glia 2002; 38: 137–145.Google Scholar
Asimakopoulos G, Thompson R, Nourshargh S, et al. An anti-inflammatory property of aprotinin detected at the level of leukocyte extravasation. J Thorac Cardiovasc Surg 2000; 120: 361–369.Google Scholar
McEver RP. Selectins: novel receptors that mediate leukocyte adhesion during inflammation. Thromb Haemostasis 1991; 65: 223–228.Google Scholar
Abbott NJ, Revest PA, Romero IA. Astrocyte–endothelial interaction: physiology and pathology. Neuropathol Appl Neurobiol 1992; 18: 424–433.Google Scholar
Stanimirovic DB, Ball R, Durkin JP. Stimulation of glutamine uptake and Na, K-ATPase activity in rat astrocytes exposed to ischemia-like insults. Glia 1997; 19: 123–134.Google Scholar
Garcia JH, Liu KF, Relton JK. Interleukin-1 receptor antagonist decreases the number of necrotic neurons in rats with middle cerebral artery occlusion. Am J Pathol 1995; 147: 1477–1486.Google Scholar
Zhang W, Smith C, Monette R, Shapiro A, Hutchinson J, Stanimirovic D. Increased expression of bioactive chemokines in human cerebromicrovascular endothelial cells and astrocytes subjected to simulated ischemia in vitro. J Neuro-immunol 1999; 101: 148–160.Google Scholar
Stanimirovic DB, Shapiro A, Wong J, Hutchison J, Durkin JP. The induction of ICAM-I in human cerebromicrovascular endothelial cells (HCEC) by ischemic-like conditions promotes enhanced neutrophil/HCEC adhesion. J Neuroimmunol 1997; 76: 193–205.Google Scholar
Mojcik CF, Levy JH. Aprotinin and the systemic inflammatory response after cardiopulmonary bypass. Ann Thorac Surg 2001; 71: 745–754.Google Scholar
Hill GE, Alonso A, Spurzem JR, Stammers AH, Robbins RA. Aprotinin and methylprednisolone equally blunt neutrophil cardiopulmonary bypass-induced inflammation in humans. J Thorac Cardiovasc Surg 1995; 110: 1658–1662.Google Scholar
Asimakopoulos G, Lidington EA, Mason J, Haskard DO, Taylor KM, Landis RC. Effect of aprotinin on endothelial cell activation. J Thorac Cardiovasc Surg 2001; 122: 123–128.Google Scholar
Pintigny D, Prigent DJ. Aprotinin can inhibit the proteolytic activity of thrombin: a fluorescent and enzymatic study. Eur J Biochem 1992; 207: 89–95.Google Scholar
Dantzer R, Bluthe RM, Gheusi G, et al. Molecular basis of sickness behavior. Ann NY Acad Sci 1998; 856: 132–138.Google Scholar
Turrin NP, Gayle D, Ilyin SE, et al. Pro-inflammatory and anti-inflammatory cytokine mRNA induction in the periphery and brain following intraperitoneal administration of bacterial lipopolysaccharide. Brain Res Bull 2001; 54: 443–453.Google Scholar
Vallieres L, Rivest S. Interleukin-6 is a needed proinflammatory cytokine in the prolonged neural activity and transcriptional activation of corticotrophin-releasing factor during endotoxemia. Endocrinology 1999; 140: 3890–3903.Google Scholar
Nadeau S, Rivest S. The complement system is an integrated part of the natural innate immune response in the brain. FASEB J 2001; 15: 1410–1412.Google Scholar
Lacroix S, Rivest S. Effect of acute systemic inflammatory response and cytokines on the transcription of the genes encoding cyclooxygenase enzymes (COX-1 and COX-2) in the rat brain. J Neurochem 1998; 70: 452–466.Google Scholar
Wong ML, Bongiorno PB, al-Shekhlee A, Esposito A, Khatri P. IL-1 beta, IL-1 receptor type I and iNOS gene expression in rat brain vasculature and perivascular areas. NeuroReport 1996; 7: 2445–2448.Google Scholar
Allan SM, Rothwell NJ. Cytokines and acute neuro degeneration. Nat Revs Neurosci 2001; 2: 734–744.Google Scholar
Paparella D, Yau TM, Young E. Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update. Eur J Cardiothorac Surg 2002; 21: 232–244.Google Scholar
del Zoppo GJ, Schmid-Schonbein GW, Mori E, Copeland BR, Chang CM. Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons. Stroke 1991; 22: 1276–1283.Google Scholar