Mechanisms of endothelial cell injury in acute inflammation.
Injury to the vascular endothelium is a critical event in acute inflammatory disease processes. In acute inflammation, endothelial cell injury is frequently mediated by activated neutrophils. The process by which activated neutrophils produce endothelial cell damage is complex. It involves generation of reactive oxygen metabolites, principally hydrogen peroxide (H2O2), and reduction of the H2O2 to the hydroxyl radical within the target cell. Hydroxyl radical generation depends on a source of superoxide anion and iron, and it appears that the target cell is the source of both. Thus, the endothelial cell actively participates in the biochemical events that lead to the formation of the toxic radical. Although neutrophil oxidants play a major role in injury, other neutrophil products, released from granules during activation, also contribute to injury. In addition to neutrophil products, other moieties 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 some conditions and may potentiate neutrophil-mediated injury under others. Like injury resulting from activated neutrophils, cytokine-induced endothelial cell injury also appears to involve generation of reactive oxygen metabolites within the target cells. Finally, endothelial cells become susceptible to injury as they age in vitro. The mechanism by which spontaneous injury occurs in aging cells appears to be significantly different from that responsible for neutrophil-induced and cytokine-induce injury. Age-related injury resembles apoptosis in a number of respects.
Varani
J
J
Ward
P A
PA
D000375:Aging / Q000502:physiology; D000818:Animals; D016207:Cytokines / Q000502:physiology; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology*; D008954:Models, Biological; D009504:Neutrophils / Q000502:physiology*; D016877:Oxidants / Q000378:metabolism
D016207:Cytokines; D016877:Oxidants; D006861:Hydrogen Peroxide