Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Jan 1995
Adhesion molecule mediated endothelial cell injury elicited by activated leukocytes.
To clarify the mechanism of vascular endothelial cell injury induced by activated leukocytes, we examined the effects of antibodies against adhesion molecules on the injury and on the intracellular peroxide level in endothelial cells. Treatment of leukocytes with phorbol myristate acetate (PMA) caused significant increases in the expression of adhesion molecules, CD11a, CD11b, CD11c, and CD18, on the surface of the leukocytes. Monoclonal antibodies against CD11a, CD11b and CD18, and ICAM-1, an adhesion molecule in the side of endothelial cells, abolished significantly the endothelial cell injury induced by PMA-stimulated leukocytes. ⋯ Both events were only partially blocked by catalase (approximately 40%), but almost completely abolished by deferoxamine, a chelator of ferrous ions, suggesting that hydroxyl radicals produced in endothelial cells themselves from xanthine oxidase may injure the cells from their inside. Therefore, the effect of allopurinol, a specific inhibitor of xanthine oxidase, was examined. Pretreatment of endothelial cells with allopurinol caused significant but not complete inhibition (approximately 60%) of both the early and the late events, suggesting that influx of hydrogen peroxide may also be important.(ABSTRACT TRUNCATED AT 400 WORDS)