Title: 93. Differential Regulation of Skeletal Muscle Regeneration and Angiogenesis by CCR2 Activating Chemokines
Abstract: Objective(s): The CC chemokine receptor 2 (CCR2) is essential for macrophage recruitment and macrophages play important roles in angiogenesis and muscle regeneration. We have previously demonstrated that CCR2 −/− mice exhibit severe impairments in macrophage recruitment in conjunction with altered angiogenesis and muscle regeneration after skeletal muscle injury. However, multiple chemokines, including monocyte chemotactic protein (MCP)-1, MCP-3 and MCP-5 activate CCR2. This study measured muscle regeneration, angiogenesis and MCP-5 levels in wild type (WT) and MCP-1 −/− mice to define the relative contribution of MCP-1 to the impairments previously observed in CCR2 −/− mice. Methods: Injury was induced following cardiotoxin (CT) injection into hind limb muscles of MCP-1 −/− or WT mice (C57Bl/6J background). Flow cytometry was used to estimate numbers of tissue macrophages (CD11b+/Gr−1−) at post-CT days 3 and 7. Muscle fiber cross-sectional area (CSA) and capillary density (capillaries/mm2) were assessed by histomorphometry at baseline (no injury) and at various times after injury. Tissue MCP-5 levels were quantified in muscle protein extracts by ELISA. Results: Maximal macrophage recruitment occurred 3 days post-CT in both strains, however, macrophages in MCP-1 −/− mice were significantly (p=0.007) decreased compared to WT (16±3 vs 35±5 macrophage/g tissue; mean±SEM, n=5/group); macrophage numbers were comparable in both mouse groups at day 7. While baseline fiber CSA was similar in both strains, MCP-1 −/− mice had significantly decreased regenerating fiber CSA at all post-CT time points compared to WT mice (Fig A). Despite the impairment in regenerated fiber CSA in MCP-1 −/− mice, capillary density was comparable in both groups at baseline and post-CT days 14, 21 and 28. Baseline levels of MCP-5 were barely detectable in both strains. While both strains exhibited significantly increased MCP-5 levels compared to baseline at 1 and 3 days post-injury, MCP-5 levels were significantly elevated (p=0.03) in MCP-1 −/− mice compared to WT mice at day 3 (Fig B).
Publication Year: 2008
Publication Date: 2008-02-01
Language: en
Type: article
Indexed In: ['crossref']
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