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The Requirement of CC‐Chemokine Receptor‐2 (CCR2) Expression by Bone Marrow‐Derived Cells (BMCs) for Arteriogenesis is Stimulus Dependent
Author(s) -
Nickerson Meghan M,
Song Ji,
Owens Gary K,
Skalak Thomas C,
Price Richard J
Publication year - 2008
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.22.1_supplement.1147.14
Subject(s) - arteriogenesis , hindlimb , ccr2 , ischemia , medicine , bone marrow , chemokine , ccl2 , stromal cell derived factor 1 , endocrinology , chemokine receptor , chemistry , inflammation , cxcr4
The MCP‐1/CCR2‐mediated recruitment of BMCs is necessary for hindlimb arteriogenesis in Balb/C mice, but not in C57BL/6 mice. Here, we tested whether a stronger inflammatory stimulus is needed to trigger CCR2‐dependent arteriogenesis in the C57BL/6 strain. We implanted dorsal skinfold window chambers (WCs) or created hindlimb ischemia in C57BL/6 wild‐type (WT) mice engrafted with either CCR2 −/− BMCs (CCR2 −/− >WT) or WT BMCs (WT>WT). In WT mice, 1 day after stimulation, MCP‐1 levels rose from “undetectable” to 463 pg/mg in WC tissue but only 17.0 pg/mg in ischemic hindlimb. WC implantation elicited a 66% (28 μm) increase in maximum arteriolar diameter over 7 days in WT>WT mice; however, CCR2 −/− >WT mice exhibited no arteriogenesis (−0.5%; −2μm). CD11b staining confirmed diminished monocyte recruitment in CCR2 −/− >WT WCs. Hindlimb ischemia created strong arteriogenesis responses in both CCR2 −/− >WT and WT>WT mice, confirming that CCR2 expression by BMCs is not required for arteriogenesis in this model. We conclude that the requirement for CCR2 expression by BMCs in arteriogenesis is stimulus‐dependent and correlated to the degree of tissue inflammation. Supported by NIH HL65958 and NIH HL74082.