期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 202, 期 3, 页码 363-369出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20050986
关键词
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资金
- NCRR NIH HHS [P41 RR000954, P41 RR 00954] Funding Source: Medline
- NIGMS NIH HHS [T32 GM 08795, T32 GM008795] Funding Source: Medline
DAP12 ( KARAP) is a transmembrane signaling adaptor for a family of innate immunoreceptors that have been shown to activate granulocytes and monocytes/macrophages, amplifying production of inflammatory cytokines. Contrasting with these data, recent studies suggest that DAP12 signaling has an inhibitory role in the macrophage response to microbial products ( Hamerman, J.A., N.K. Tchao, C.A. Lowell, and L.L. Lanier. 2005. Nat. Immunol. 6:579-586). To determine the in vivo role for DAP12 signaling in inflammation, we measured the response of wild-type (WT) and DAP12(-/-) mice to septic shock. We show that DAP12(-/-) mice have improved survival from both endotoxemia and cecal ligation and puncture induced septic shock. As compared with WT mice, DAP12(-/-) mice have decreased plasma cytokine levels and a decreased acute phase response during sepsis, but no defect in the recruitment of cells or bacterial control. In cells isolated after sepsis and stimulated ex vivo, DAP12 signaling augments lipopolysaccharide-mediated cytokine production. These data demonstrate that, during sepsis, DAP12 signaling augments the response to microbial products, amplifying inflammation and contributing to mortality.
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