Department of Pathology
Cell Biology | Cells | Cellular and Molecular Physiology | Hemic and Immune Systems | Immunopathology | Pathological Conditions, Signs and Symptoms | Pathology
When cells die by necrosis in vivo they stimulate an inflammatory response. It is thought that this response is triggered when the injured cells expose proinflammatory molecules, collectively referred to as damage associated molecular patterns (DAMPs), which are recognized by cells or soluble molecules of the innate or adaptive immune system. Several putative DAMPs and/or their receptors have been identified, but whether and how much they participate in responses in vivo is incompletely understood, and they have not previously been compared side-by-side in the same models. This study focuses on evaluating the contribution of multiple mechanisms that have been proposed to or potentially could participate in cell death-induced inflammation: The third component of complement (C3), ATP (and its receptor P2X7), antibodies, the C-type lectin receptor Mincle (Clec4e), and protease-activated receptor 2 (PAR2). We investigate the role of these factors in cell death-induced inflammation to dead cells in the peritoneum and acetaminophen-induced liver damage. We find that mice deficient in antibody, C3 or PAR2 have impaired inflammatory responses to dying cells. In contrast there was no reduction in inflammation to cell death in the peritoneum or liver of mice that genetically lack Mincle, the P2X7 receptor or that were treated with apyrase to deplete ATP. These results indicate that antibody, complement and PAR2 contribute to cell death-induced inflammation but that Mincle and ATP- P2X7 receptor are not required for this response in at least 2 different in vivo models.
Inflammation, Cell death, Neutrophils, Monocytes, Complement activation, Necrotic cell death, Peritoneum, Necrosis
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DOI of Published Version
PLoS One. 2014 Aug 15;9(8):e104741. doi: 10.1371/journal.pone.0104741. eCollection 2014. Link to article on publisher's site
Kataoka, Hiroshi; Kono, Hajime; Patel, Zubin; and Rock, Kenneth L., "Evaluation of the contribution of multiple DAMPs and DAMP receptors in cell death-induced sterile inflammatory responses" (2014). Open Access Articles. 2477.
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