Premium
Role of scavenger receptor MARCO in macrophage responses to CpG oligodeoxynucleotides
Author(s) -
Józefowski Szczepan,
Sulahian Timothy H.,
Arredouani Mohamed,
Kobzik Lester
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0705357
Subject(s) - cpg oligodeoxynucleotide , biology , scavenger receptor , tlr9 , receptor , cpg site , microbiology and biotechnology , macrophage , biochemistry , in vitro , gene , dna methylation , gene expression , lipoprotein , cholesterol
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.