DYNAMICS OF THE STRESS- AND FAS-SNDUCED APOPTOSSS OF HUMAN NEUTROPHILS UNDER THE ACTION OF ENDOTOXINS

摘要

Endotoxin interaction with neutrophils that play the key role in innate immunity is extremely important at the initial stages of Gram-negative sepsis and endotoxin shock. During sepsis and in vitro, endotoxins inhibit apoptosis of neutrophils. The LPS-dependent regulation of neutrophii apoptosis depends on mitogen-activated protein kinases, including p38-mitogen-activated protein kinases (p38MAPK) and extracellular signal-regulated kinases (ERK). Interaction between the p38MAPK- and ERK signal pathways may influence sepsis development. Phosphatidylinositol-3 kinase (PI-3K) also participates in neutrophii activation and regulation of their apoptosis. Targeted control of neutrophii apoptosis during inflammation is now considered a promising approach to the recovery of cell homeostasis in treatment of sepsis and other pathological states. We studied the dynamics of the effects of monoclonal anti-Fas-antibodies and ultraviolet radiation (UVC) on the regulation of neutrophii apoptosis in the presence of endotoxins. We aimed at studying the individual pathways of intracellular signalling that regulates apoptosis under the action of endotoxins, anti-Fas- monoclonal antibodies (anti-Fas-AB), and UVC. The results of the inhibition analysis showed that ERK participate only in the LPS-induced inhibition of neutrophii apoptosis, but not in the apoptosis activation caused by UVC and anti-Fas-ABs. p38MAPK participates in the regulation of UVC-induced apoptosis, as well as in the regulation of apoptosis under the action of endotoxins. PI-3K contributes more to the regulation of the anti-Fas-AB-activated apoptosis than to that of the UVC-induced apoptosis.