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DAP12 (KARAP) amplifies inflammation and increases mortality from endotoxemia and septic peritonitis.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2005 Aug 01; Vol. 202 (3), pp. 363-9. - Publication Year :
- 2005
-
Abstract
- 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.
- Subjects :
- Acute-Phase Reaction genetics
Acute-Phase Reaction metabolism
Acute-Phase Reaction mortality
Adaptor Proteins, Signal Transducing genetics
Animals
Cytokines metabolism
Endotoxemia genetics
Endotoxemia mortality
Granulocytes metabolism
Mice
Mice, Knockout
Peritonitis genetics
Peritonitis mortality
Sepsis genetics
Sepsis mortality
Adaptor Proteins, Signal Transducing metabolism
Endotoxemia metabolism
Macrophages metabolism
Peritonitis metabolism
Sepsis metabolism
Signal Transduction genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1007
- Volume :
- 202
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 16061725
- Full Text :
- https://doi.org/10.1084/jem.20050986