title: Disparate regulation and function of the class A scavenger receptors SR-AI/II and MARCO.
abstract: The macrophage class A scavenger receptors, macrophage receptor with a collagenous structure (MARCO) and type I/II class A scavenger receptor (SR-AI/II), share structural features and roles in host defense, but little is known about their regulation and signaling properties. Ligation of MARCO on mouse thioglycollate-elicited peritoneal macrophages (PEMs) with immobilized mAb costimulated IL-12 production, in contrast to previously reported inhibition by SR-AI/II. PEMs from MARCO-deficient mice exhibited 2.7 times lower IL-12 production in responses to stimulation with LPS and IFN-gamma and lack of significant IL-12 production on stimulation with LPS alone. Conversely, SR-AI/II-deficient PEMs produced 2.4 and 1.8 times more IL-12 than wild-type PEMs in response to LPS or LPS and IFN-gamma, respectively. Corresponding differences in regulation of SR-A and MARCO expression were also observed. Th1 adjuvants (LPS, a CpG motif-containing oligodeoxynucleotide (CpG-ODN), IL-12, and GM-CSF) increased, whereas Th2-polarizing factors (IL-4, M-CSF, and non-CpG ODN) decreased expression of MARCO on J774 macrophage-like cells. Expression of SR-A was regulated in the opposite manner to MARCO or not affected. Whereas MARCO was involved in opsonin-independent phagocytosis in CpG-ODN-pretreated but not in IL-4-pretreated J774 cells, anti-SR-A Abs inhibited particle uptake in untreated and IL-4-pretreated but not in CpG-ODN-pretreated cells. SR-A and MARCO are regulated differently and mediate distinct negative and positive effects on IL-12 production in macrophages. These differences may contribute to sustained Th1 or Th2 polarization of ongoing immune responses.
authors.affiliation: Physiology Program, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Szczepan
authors.initials: S
authors.lastname: Józefowski
authors.forename: Mohamed
authors.initials: M
authors.lastname: Arredouani
authors.forename: Timothy
authors.initials: T
authors.lastname: Sulahian
authors.forename: Lester
authors.initials: L
authors.lastname: Kobzik
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000276:immunology*; D007109:Immunity; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051117:Scavenger Receptors, Class A / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; C092228:Marco protein, mouse; D011971:Receptors, Immunologic; D051117:Scavenger Receptors, Class A; D018664:Interleukin-12