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Chemokines and traumatic muscle injury.

Simeonova PP; Warren GL; Hulderman T; McKinstry M; Summan M

Chemokines and Chemokine Receptors, Breckenridge, Colorado, January 7-12, 2003. Richmond, CA: Berlex Biosciences, 2003 Jan; :60

20027493

Skeletal muscle injuries are associated with local infiltration of large numbers of mononuclear cell, degeneration of the injured myofibers and removal of the cell debris by phagocytosis. In parallel with these events, quiescent muscle precursor cells (satellite cells), are activated. The activated satellite cells proliferate, migrate and fuse with other cells to form new multinucleated myotubest and eventually replace the disrupted myofibers. A great deal of efforts has been focused on trying to understand the cellular and molecular mechanisms of injury demarcation and activation of the repair processes, which are unique for the skeletal muscle (e.g. this phenomenon does not occur completely in the cardiac muscle). We hypothesize that early inflammatory mediators, such as chemokines, are released during the muscle disruption and degeneration and are involved in macrophage recruitment and satellite cell migration and activation. Using gene expression methodology (RNAase protection assay and real-time PCR) in a mouse model (freeze injury of Tibialis anterior muscle, TA)t we demonstrated an expression of MCP-l and MIP-l p in the first 24 hrs postinjury. The major receptors for these chemokines. CCRl and CCR5, were colocalized, through immunostaining analysis, with mac-3, a marker of activated macrophages and myogenin, a transcription factor involved in satellite cell activation. Down-regulation of MCP-l and MIP-l J3 responses by application of CCR5 deficient mice and MCP-l neutralizing antibody, resulted in minimal effects in inflammatory cell influx but a significant delay in muscle function recovery. Further, using in vitro model, C2C12, a myoblast cell line, we demonstrated that satellite cells express CCR2 and CCRS receptors and these chemokine pathways are involved in satellite cell migration activity. In conclusion, the present study delineates a role of the chemokine network in the mechanisms of regeneration of skeletal muscle after traumatic injury.

Injuries; Musculoskeletal-system-disorders; Skeletal-system-disorders; Skeletal-disorders; Muscle-function; Traumatic-injuries; Laboratory-animals

20030108

Abstract; Conference/Symposia Proceedings

2003

HELD

Chemokines and Chemokine Receptors, Breckenridge, Colorado, January 7-12, 2003

WV; CA; CO; GA