Role of CC chemokines in skeletal muscle functional restoration after injury.

The purpose of this study was to determine whether certain chemokines, which are highly expressed in injured skeletal muscle, are involved in the repair and functional recovery of the muscle after traumatic injury. In wild-type control mice, mRNA transcripts of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1 as well as their major receptors, CCR5 and CCR2, increased after freeze injury and gradually returned to control (uninjured) levels by 14 days. Muscle function and histological characteristics were monitored in injured mice that were genetically deficient for the CCR5 receptor (a major receptor for MIP-1alpha and MIP-1beta) and also rendered MCP-1 deficient with neutralizing antibodies. To dissect the role of these chemokines, additional studies were conducted in CCR5- and CCR2-deficient mice. CCR5-/- mice injected with MCP-1 antiserum for the first 3 days after injury exhibited a twofold greater maximal isometric tetanic torque deficit at 14 days after injury than did controls (i.e., 33% vs. 17%; P = 0.002). The impaired functional recovery was accompanied with an increased fat infiltration within the regenerating muscle without a significant difference in the influx of inflammatory cells, including macrophages. Strength recovery was also impaired in mice deficient for the receptor of MCP-1, CCR2, but not in CCR5-/- mice that were not injected with MCP-1 antiserum. The data suggest that MCP-1/CCR2 plays a role in the regeneration and recovery of function after traumatic muscle injury.