{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:10:41Z","timestamp":1793293841961,"version":"4.5.0"},"reference-count":38,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2010,9]]},"abstract":"<jats:p>Muscle regeneration requires CC chemokine receptor 2 (CCR2) expression on bone marrow-derived cells; macrophages are a prominent CCR2-expressing cell in this process. CCR2\u2212\/\u2212 mice have severe impairments in angiogenesis, macrophage recruitment, and skeletal muscle regeneration following cardiotoxin (CTX)-induced injury. However, multiple chemokines activate CCR2, including monocyte chemotactic proteins (MCP)-1, -3, and -5. We hypothesized that MCP-1 is the chemokine ligand that mediates the impairments present in CCR2\u2212\/\u2212 mice. We examined muscle regeneration, capillary density, and cellular recruitment in MCP-1\u2212\/\u2212 and CCR2\u2212\/\u2212 mice following injury. Muscle regeneration and adipocyte accumulation, but not capillary density, were significantly impaired in MCP-1\u2212\/\u2212 compared with wild-type (WT) mice; however, muscle regeneration and adipocyte accumulation impairments were not as severe as observed in CCR2\u2212\/\u2212 mice. Although tissue levels of MCP-5 were elevated in MCP-1\u2212\/\u2212 mice compared with WT, the administration of MCP-5 neutralizing antibody did not alter muscle regeneration in MCP-1\u2212\/\u2212 mice. While neutrophil accumulation after injury was similar in all three mouse strains, macrophage recruitment was highest in WT mice, intermediate in MCP-1\u2212\/\u2212 mice, and severely impaired in CCR2\u2212\/\u2212 mice. In conclusion, while the absence of MCP-1 resulted in impaired macrophage recruitment and muscle regeneration, MCP-1\u2212\/\u2212 mice exhibit an intermediate phenotype compared with CCR2\u2212\/\u2212 mice. Intermediate macrophage recruitment in MCP-1\u2212\/\u2212 mice was associated with similar capillary density to WT, suggesting that fewer macrophages may be needed to restore angiogenesis vs. muscle regeneration. Finally, other chemokines, in addition to MCP-1 and MCP-5, may activate CCR2-dependent regenerative processes resulting in an intermediate phenotype in MCP-1\u2212\/\u2212 mice.<\/jats:p>","DOI":"10.1152\/ajpregu.00797.2009","type":"journal-article","created":{"date-parts":[[2010,7,15]],"date-time":"2010-07-15T03:08:11Z","timestamp":1279163291000},"page":"R832-R842","source":"Crossref","is-referenced-by-count":152,"title":["Regulation of skeletal muscle regeneration by CCR2-activating chemokines is directly related to macrophage recruitment"],"prefix":"10.1152","volume":"299","author":[{"given":"Carlo O.","family":"Martinez","sequence":"first","affiliation":[{"name":"Departments of 1Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"McHale","sequence":"additional","affiliation":[{"name":"Departments of 1Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason T.","family":"Wells","sequence":"additional","affiliation":[{"name":"Departments of 1Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Ochoa","sequence":"additional","affiliation":[{"name":"Departments of 1Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel E.","family":"Michalek","sequence":"additional","affiliation":[{"name":"Departments of 1Surgery,"},{"name":"Epidemiology and Biostatistics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda M.","family":"McManus","sequence":"additional","affiliation":[{"name":"Pathology, and"},{"name":"Periodontics, and"},{"name":"Sam and Ann Barshop Institute for Longevity and Aging Studies, at the University of Texas Health Science Center San Antonio; 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