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Induction of CXCR7 Switches SDF‐1 Signaling and Phagocytic Function in Macrophages: a Potential Role in Atherosclerosis
Author(s) -
Ma Wanshu,
Liu Yiwei,
Ellison Nicholas,
Shen Jianzhong
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1096.3
Subject(s) - macrophage , microbiology and biotechnology , p38 mitogen activated protein kinases , signal transduction , mapk/erk pathway , chemistry , monocyte , receptor , gene silencing , cancer research , biology , immunology , in vitro , biochemistry , gene
Objective The discovery of CXCR7 as a new receptor for SDF‐1 places many previously described SDF‐1 functions attributed to CXCR4 in question, though whether CXCR7 acts as a signaling or “decoy” receptor has been in debate. It is known that CXCR7 is not expressed in normal blood leukocytes; however, the potential role of leukocyte CXCR7 in disease states has not been addressed. Methods and Results We show that CXCR7 was detected in macrophage‐positive area of aortic atheroma of ApoE‐null mice, but not in healthy aorta. During monocyte‐to‐macrophage differentiation, CXCR7 was up‐regulated at mRNA and protein levels, with more expression in M1 than in M2 phenotype. In addition, CXCR7 induction was associated with a SDF‐1 signaling switch from pro‐survival ERK and AKT pathways in monocytes to pro‐inflammatory JNK and p38 pathways in macrophages. The latter effect was mimicked by a CXCR7‐selective agonist TC14012 and abolished by siRNA knockdown of CXCR7. Furthermore, CXCR7 activation increased macrophage phagocytic activity, which was suppressed by CXCR7 siRNA silencing or by inhibiting either the JNK or p38 pathways. Conclusions CXCR7 is induced during monocyte‐to‐macrophage differentiation, which is required for SDF‐1 signaling to JNK and p38 pathways, leading to enhanced macrophage phagocytosis, thus possibly contributing to atherogenesis.