Complement-induced impairment of innate immunity during sepsis

被引：150

作者：

Huber-Lang, MS ^{[1
]}

Younkin, EM ^{[1
]}

Sarma, JV ^{[1
]}

McGuire, SR ^{[1
]}

Lu, KT ^{[1
]}

Guo, RF ^{[1
]}

Padgaonkar, VA ^{[1
]}

Curnutte, JT ^{[1
]}

Erickson, R ^{[1
]}

Ward, PA ^{[1
]}

机构：

[1] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA

来源：

JOURNAL OF IMMUNOLOGY | 2002年 / 169卷 / 06期

关键词：

D O I：

10.4049/jimmunol.169.6.3223

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

This study defines the molecular basis for defects in innate immunity involving neutrophils during cecal ligation/puncture (CLP)-induced sepsis in rats. Blood neutrophils from CLP rats demonstrated defective phagocytosis and defective assembly of NADPH oxidase, the latter being due to the inability of p47(phox) to translocate from the cytosol to the cell membrane of neutrophils after cell stimulation by phorbol ester (PMA). The appearance of these defects was prevented by in vivo blockade of C5a in CLP rats. In vitro exposure of neutrophils to C5a led to reduced surface expression of C5aR and defective assembly of NADPH oxidase, as defined by failure in phosphorylation of p47(phox) and its translocation to the cell membrane, together with failure in phosphorylation of p42/p44 mitogen-activated protein kinases. These data identify a molecular basis for defective innate immunity involving neutrophils during sepsis.

引用

页码：3223 / 3231

页数：9

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