In vivo regulation of neutrophil apoptosis by C5a during sepsis

Journal of Leukocyte Biology

Firas S. Zetoune¹  Hongwei Gao¹  Daniel Rittirsch¹  Ren-Feng Guo¹  Kevin X. Shi¹  Lei Sun¹  Peter A. Ward¹  Vidya J. Sarma¹ 

[1] University of Michigan Medical School, Department of Pathology, Ann Arbor, Michigan, USAUniversity of Michigan Medical School, Department of Pathology, Ann Arbor, Michigan, USAUniversity of Michigan Medical School, Department of Pathology, Ann Arbor, Michigan, USA

关键词: cell signaling;    survival;    phagocyte;    inflammation;   

DOI  :  10.1189/jlb.0106065

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Delayed neutrophil apoptosis is characteristic of sepsis and may accentuate organ injury. It has been shown that PI-3K and MAPK pathways provide survival signaling in neutrophils. In this study, we demonstrate that neutrophils isolated from septic rats are resistant to apoptosis in comparison with the cells from normal animals. In contrast to normal serum, septic sera induced strong phosphorylation of AKT and p44/42 in neutrophils obtained from normal rats, resulting in marked resistance of these cells to apoptosis. Protection from apoptosis by septic sera was abrogated completely by inhibition of PI-3K and partially diminished by MEK inhibition. Increased neutrophil survival in septic rats was associated with increased levels of Bcl-xL in neutrophils and decreased levels of Bim expression. In vivo blockade of C5a in cecal ligation and puncture rats by anti-C5a antibody markedly restored the susceptibility of neutrophils to undergo apoptosis. C5a activated AKT and p44/42 and also enhanced X-linked inhibitor of apoptosis expression in neutrophils. LPS and C5a were able to induce Bcl-xL expression. Thus, neutrophil survival signals derived from effects of septic sera could be linked to activation of ERK1/2 and PI-3K, increased antiapoptotic protein expression, and ultimately, delayed neutrophil apoptosis.

【 授权许可】

Unknown