title: The class A scavenger receptor SR-A/CD204 and the class B scavenger receptor CD36 regulate immune functions of macrophages differently.
abstract: SR-A/CD204 and CD36 are major receptors responsible for oxidized lipoproteins uptake by macrophages in atherosclerotic plaques. Both receptors also share the role as receptors for different pathogens, but studies on their signaling have been hampered by the lack of selective ligands. We report that, upon specific ligation by Ab, SR-A does not induce cytokine production, but mediates inhibition of LPS-stimulated production of IL-6 and IL-12/23p40, enhancement of IL-10 release, and has no effect on TNF-α and RANTES production in murine macrophages. In contrast, anti-CD36 Ab alone stimulated production of all these cytokines, with IL-10 production being exceptionally high. Effects of anti-CD36 Ab, except of IL-10 production, were mediated by CD14 and TLR2, whereas those of SR-A ligation by heterotrimeric Gi/o proteins and by phosphatidylinositol 3-kinases. Surprisingly, we found that LPS uptake by macrophages was mediated in part by CD36 cooperating with CD14, whereas SR-A was not involved in this process. Finely, during in vitro Ag presentation to naïve CD4(+) lymphocytes, pre-incubation of macrophages with anti-CD36 Ab enhanced IFN-γ production in the co-culture, but exerted the opposite effect under conditions enabling IL-10 accumulation. In contrast, anti-SR-A Ab was ineffective alone, but reversed the Th1-polarizing effect of LPS.
authors.affiliation: Department of Immunology, Jagiellonian University Medical College, Krakow, Poland szjozefowski@poczta.onet.pl.
authors.forename: Szczepan
authors.initials: S
authors.lastname: Józefowski
authors.affiliation: Department of Immunology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Biedroń
authors.affiliation: Department of Immunology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Sróttek
authors.affiliation: Department of Evolutionary Immunology, Jagiellonian University, Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Chadzińska
authors.affiliation: Department of Immunology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Marcinkiewicz
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007111:Immunity, Cellular / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000187:drug effects; D008264:Macrophages / Q000276:immunology* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D037342:Pertussis Toxin / Q000494:pharmacology; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000187:drug effects; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D018955:CD36 Antigens; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; C495140:Msr1 protein, mouse; D051117:Scavenger Receptors, Class A; D051195:Toll-Like Receptor 2; D037342:Pertussis Toxin; D000077191:Wortmannin
keywords: Acetylated LDL; Pam3CSK4 lipopeptide; dextran sulfate; lipoteichoic acid; polarization of immune responses