Enhancement of apoptosis in cerebral endothelial cells by selected inflammatory signals.

Abstract

Acute inflammation is characterized by (1) microvascular injury attracting acute inflammatory cells (mostly polymorphonuclear neutrophils (PMNs) and macrophages), (2) plasma extravasation leading to swelling, and (3) edema in the inflamed site and tissue destruction.' The accumulation of PMNs and macrophages in the acutely inflamed tissue results from activation and injury of endothelial cells (ECs). PMN-EC and/or macrophage-EC interaction perpetuates progressive vascular injury, edema formation, and tissue injury. In inflammatory reactions, the potential pathogenetic roles of ECs have been increasingly recognized.? Interaction between ECs and PMNs/macrophages in acute inflammation is mediated by a number of inflammatory mediator^.^,' The recruitment of circulating PMNs and macrophages into the inflammatory foci involves the expression of adhesive molecules on ECs, PMNs, and macrophages. Interaction between PMNs/macrophages and ECs engage such inflammatory mediators as cytokines, free radicals, eicosanoids, kinins, and others (e.g., histamines and serotonin). Nitric oxide (NO) has emerged to be a key inflammatory mediator. Proinflammatory actions of NO are at least partly related to the formation of free radicals, such as per~xynitrite.~,~ In this communication, we summarize recent findings from our laboratory on the effects of inflammatory mediators, especially the free radicals and cytokines, on endothelial function in vitro.