title: Deletion of scavenger receptor A gene in mice resulted in protection from septic shock and modulation of TLR4 signaling in isolated peritoneal macrophages.
abstract: Scavenger receptor A (Sra), also known as macrophage scavenger receptor 1 (Msr1), is a surface glycoprotein preferentially present in macrophages that plays a primary role in innate immunity. Previous studies have shown that Sra is a modifier gene for the response to bacterial LPS in mice at the level of IL-10 production, in particular. In the present study, we found that Sra(-/-) mice are more resistant to septic shock induced by cecal ligation and puncture than wild-type C57BL/6 J (B6) mice. In addition, Sra(-/-) mice displayed initial elevated high density lipoprotein (HDL) circulating levels. Naïve peritoneal macrophages (PMs) were isolated from Sra(-/-) mice to understand the possible protective mechanism. Incubation of these cells with LPS was found to modulate TLR4 signaling, leading to a reduction in IL-10 and IL-6 mRNA levels, but not TNF-α expression, at low concentrations of LPS in comparison with PMs isolated from B6 mice. No differences were found in LPS binding between PMs derived from Sra(-/-) or B6 mice. The lack of Sra binding to LPS was confirmed after transfection of Chinese hamster ovary (CHO) cells with the Sra gene. The contribution of Sra to the outcome of sepsis may be a combination of changes in TLR4 signaling pathway and elevated levels of HDL in circulation, but also LPS toxicity.
authors: MSTP program Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors: Robert
authors: R
authors: Drummond
authors: David M
authors: DM
authors: Cauvi
authors: Dennis
authors: D
authors: Hawisher
authors: Donghuan
authors: D
authors: Song
authors: Diego F
authors: DF
authors: Niño
authors: Raul
authors: R
authors: Coimbra
authors: Stephen
authors: S
authors: Bickler
authors: Antonio
authors: A
authors: De Maio
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism*; D012772:Shock, Septic / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D051117:Scavenger Receptors, Class A; D051197:Toll-Like Receptor 4