Role of scavenger receptor MARCO in macrophage responses to CpG oligodeoxynucleotides.
The macrophage Class A scavenger receptor MARCO (macrophage receptor with a collagenous structure) functions as a pattern-recognition receptor for bacterial components, but its role in responses to CpG oligonucleotide sequences (CpG-ODN) in microbial DNA has not been characterized. Phosphorothioate (PS)-linked CpG-ODN stimulated IL-12 and NO production in wild-type but not in MARCO-deficient, thioglycollate-elicited peritoneal macrophages. MARCO and the related class A receptor SR-A belong to a redundant system of receptors for PS ODNs. The ability of MARCO to bind CpG-ODNs and conversely, to costimulate IL-12 and NO production upon specific ligation with immobilized mAb is consistent with MARCO being a signaling receptor for CpG-ODNs, costimulating TLR9-mediated NO and IL-12 production in macrophages. In contrast to MARCO, SR-A is likely to mediate negative regulation of macrophage responses to CpG-ODNs. In particular, increased affinity toward SR-A may contribute to decreased potency of oligo G-modified CpG-ODNs in stimulating IL-12 production. The results suggest that differential involvement of activating and inhibitory membrane receptors, such as SR-A and MARCO, may underlie profound differences observed in biological activities of different ODN sequences.
Józefowski
Szczepan
S
Physiology Program, Harvard School of Public Health, Boston, MA 02115, USA.
Sulahian
Timothy H
TH
Arredouani
Mohamed
M
Kobzik
Lester
L
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018664:Interleukin-12 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000172:deficiency / Q000502:physiology*; D051117:Scavenger Receptors, Class A / Q000172:deficiency / Q000502:physiology*; D013329:Structure-Activity Relationship
C408982:CPG-oligonucleotide; C092228:Marco protein, mouse; D009838:Oligodeoxyribonucleotides; D011971:Receptors, Immunologic; D051117:Scavenger Receptors, Class A; D018664:Interleukin-12; D009569:Nitric Oxide