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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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