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Originally published online as doi:10.1189/jlb.0705357 on August 1, 2006

Published online before print August 1, 2006
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(Journal of Leukocyte Biology. 2006;80:870-879.)
© 2006 by Society for Leukocyte Biology

Role of scavenger receptor MARCO in macrophage responses to CpG oligodeoxynucleotides

Szczepan Józefowski, Timothy H. Sulahian, Mohamed Arredouani and Lester Kobzik1

Physiology Program, Harvard School of Public Health, Boston, Massachusetts

1 Correspondence: Physiology Program, Harvard School of Public Health, 665 Huntington Avenue, SPH-2, Room 221, Boston, MA 02115. E-mail: lkobzik{at}hsph.harvard.edu

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.

Key Words: oligonucleotides • interleukin-12 • nitric oxide




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