Apoptotic Cells Protect Mice against Lipopolysaccharide-Induced Shock

Yi Ren, Yi Xie, Guoping Jiang, Jianqing Fan, Joseph Yeung, Wen Li, Paul K. H. Tam, John Savill

Research output: Contribution to journalArticlepeer-review

Abstract

LPS is a main causative agent of septic shock. There is a lack of effective therapies. In vitro studies have shown that uptake of apoptotic cells actively inhibits the secretion by activated macrophages (M phi) of proinflammatory mediators such as TNF-alpha and that such uptake increases the antiinflammatory and inummosuppressive cytokine TGF-beta. We therefore investigated the protective effect of apoptotic cells against LPS-induced endotoxic shock in mice. The current report is the first study to demonstrate that administration of apoptotic cells can protect mice from LPS-induced death, even when apoptotic cells were administered 24 h after LPS challenge. The beneficial effects of administration of apoptotic cells included 1) reduced circulating proinflammatory cytokines, 2) suppression of polymorphonuclear neutrophil infiltration in target organs, and 3) decreased serum LPS levels. LPS can quickly bind to apoptotic cells and these LPS-coated apoptotic cells can be recognized and cleared by M phi in a CD14/thrombospondin/vitronectin receptor-dependent manner, accompanied with suppression of TNF-a and enhancement of IL-10 expression by LPS-activated M phi. Apoptotic cells may therefore have therapeutic potential for the treatment of septic shock.

Original languageEnglish
Pages (from-to)4978-4985
Number of pages8
JournalJournal of Immunology
Volume180
Issue number7
Publication statusPublished - 1 Apr 2008

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