Disparate regulation and function of the class A scavenger receptors SR-AI/II and MARCO

J Immunol. 2005 Dec 15;175(12):8032-41. doi: 10.4049/jimmunol.175.12.8032.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Gene Expression Regulation / immunology*
  • Immunity
  • Interleukin-12 / biosynthesis
  • Lipopolysaccharides / pharmacology
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Mice, Knockout
  • Phagocytosis
  • Receptors, Immunologic / deficiency
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology*
  • Scavenger Receptors, Class A / deficiency
  • Scavenger Receptors, Class A / genetics
  • Scavenger Receptors, Class A / physiology*
  • Th1 Cells / metabolism
  • Th2 Cells / metabolism

Substances

  • Lipopolysaccharides
  • Marco protein, mouse
  • Receptors, Immunologic
  • Scavenger Receptors, Class A
  • Interleukin-12