MECHANISMS OF ENDOTHELIAL-CELL INJURY IN ACUTE-INFLAMMATION

Injury to the vascular endothelium is a critical event in acute inflam matory disease processes. In acute inflammation, endothelial cell inju ry is frequently mediated by activated neutrophils. The process by whi ch activated neutrophils produce endothelial cell damage is complex. I t involves generation of reactive oxygen metabolites, principally hydr ogen peroxide (H2O2), and reduction of the H2O2 to the hydroxyl radica l within the target cell. Hydroxyl radical generation depends on a sou rce of superoxide anion and iron, and it appears that the target cell is the source of both. Thus, the endothelial cell actively participate s in the biochemical events that lead to the formation of the toxic ra dical. Although neutrophil oxidants play a major role in injury, other neutrophil products, released from granules during activation, also c ontribute to injury. In addition to neutrophil products, other moietie s present at inflammatory sites, including tumor necrosis factor-alpha and interleukin-1 can also participate in injury of endothelial cells . The cytokines may be directly injurious to endothelial cells under s ome conditions and may potentiate neutrophil-mediated injury under oth ers. Like injury resulting from activated neutrophils, cytokine-induce d endothelial cell injury also appears to involve generation of reacti ve oxygen metabolites within the target cells. Finally, endothelial ce lls become susceptible to injury as they age in vitro. The mechanism b y which spontaneous injury occurs in aging cells appears to be signifi cantly different from that responsible for neutrophil-induced and cyto kine-induce injury. Age-related injury resembles apoptosis in a number of respects.