title: Apoptotic cells protect mice against lipopolysaccharide-induced shock.
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 (Mphi) of proinflammatory mediators such as TNF-alpha and that such uptake increases the antiinflammatory and immunosuppressive 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 Mphi in a CD14/thrombospondin/vitronectin receptor-dependent manner, accompanied with suppression of TNF-alpha and enhancement of IL-10 expression by LPS-activated Mphi. Apoptotic cells may therefore have therapeutic potential for the treatment of septic shock.
authors: Department of Surgery, University of Hong Kong, Hong Kong, China. ren@dls.rutgers.edu
authors: Yi
authors: Y
authors: Ren
authors: Yi
authors: Y
authors: Xie
authors: Guoping
authors: G
authors: Jiang
authors: Jianqing
authors: J
authors: Fan
authors: Joseph
authors: J
authors: Yeung
authors: Wen
authors: W
authors: Li
authors: Paul K H
authors: PK
authors: Tam
authors: John
authors: J
authors: Savill
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000187:drug effects; D012772:Shock, Septic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D019699:Thrombospondins / Q000378:metabolism
chemical_list: D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D019699:Thrombospondins