PMID- 21819344 OWN - NLM STAT- MEDLINE DCOM- 20111212 LR - 20171116 IS - 1208-6002 (Electronic) IS - 0829-8211 (Linking) VI - 89 IP - 4 DP - 2011 Aug TI - OxLDL-mediated survival of macrophages does not require LDL internalization or signalling by major pattern recognition receptors. PG - 387-95 AB - Macrophages play a key role in the pathogenesis of atherosclerosis, in part by destabilizing plaques. We and others have shown that low concentrations of oxidized LDL (oxLDL) inhibit macrophage apoptosis. As oxLDL is present in lesions, this may be a mechanism by which macrophage populations in the intima are expanded. We have previously shown that oxLDL activates prosurvival signalling pathways such as the phosphoinositide 3-kinase (PI3K) pathway in bone marrow derived macrophages (BMDMs). However, little is known about more upstream signalling events especially at the receptor level. The endocytic pattern recognition receptors (PRRs), scavenger receptor A (SR-A) and CD36, are the main receptors on macrophages for uptake of oxLDL and are therefore important in foam cell formation. The signalling PRRs such as toll-like receptor (TLR) 2 and 4 also bind some types of oxLDL. This study was done to determine if any of the known PRRs are required for the anti-apoptotic effects of oxLDL in BMDMs. To do this, we tested the effect of oxLDL on viability of BMDMs lacking both SR-A and CD36 or lacking TLR2, TLR4, CD14, FcgammaRIIb, or RAGE. Our results indicate that none of these receptors are essential for activating the oxLDL prosurvival pathway. Furthermore, we show that the anti-apoptotic effect is not dependent on the uptake of oxLDL. FAU - Riazy, Maziar AU - Riazy M AD - Department of Medicine, University of British Columbia, Vancouver, Canada. mriazy@interchange.ubc.ca FAU - Chen, Johnny H AU - Chen JH FAU - Yamamato, Yasuhiko AU - Yamamato Y FAU - Yamamato, Hiroshi AU - Yamamato H FAU - Duronio, Vincent AU - Duronio V FAU - Steinbrecher, Urs P AU - Steinbrecher UP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Canada TA - Biochem Cell Biol JT - Biochemistry and cell biology = Biochimie et biologie cellulaire JID - 8606068 RN - 0 (CD36 Antigens) RN - 0 (Fcgr2b protein, mouse) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Lipoproteins, LDL) RN - 0 (Receptor for Advanced Glycation End Products) RN - 0 (Receptors, IgG) RN - 0 (Receptors, Immunologic) RN - 0 (Scavenger Receptors, Class A) RN - 0 (Toll-Like Receptors) RN - 0 (oxidized low density lipoprotein) SB - IM MH - Animals MH - Apoptosis MH - CD36 Antigens/genetics MH - *Cell Survival MH - Cells, Cultured MH - Lipopolysaccharide Receptors/metabolism MH - Lipoproteins, LDL/metabolism/*pharmacology/physiology MH - Macrophages/drug effects/metabolism/*physiology MH - Mice MH - Mice, Knockout MH - Receptor for Advanced Glycation End Products MH - Receptors, IgG/metabolism MH - Receptors, Immunologic/metabolism MH - Scavenger Receptors, Class A/genetics MH - *Signal Transduction MH - Toll-Like Receptors/*metabolism EDAT- 2011/08/09 06:00 MHDA- 2011/12/14 06:00 CRDT- 2011/08/09 06:00 PHST- 2011/08/09 06:00 [entrez] PHST- 2011/08/09 06:00 [pubmed] PHST- 2011/12/14 06:00 [medline] AID - 10.1139/o11-035 [doi] PST - ppublish SO - Biochem Cell Biol. 2011 Aug;89(4):387-95. doi: 10.1139/o11-035.