Role of macrophages in traumatic skeletal muscle injury.
Summan-M; Hulderman-T; Matheson-JM; Simeonova-PP
FASEB J 2003 Apr; 17(7):C137
Traumatic skeletal muscle injuries result in profound histopathological changes and loss of muscle function. These injuries are associated with local infiltration of large numbers of mononuclear cells, degeneration of injured myofibres and phagocytic removal of cell debris. In the present study we evaluated the role of systemic macrophages in the injury/repair mechanisms in a traumatic skeletal muscle injury model using liposome encapsulated clodronate, a drug with well characterized monocyte/macrophage depleting qualities. C57BL/6 mice (n = 4 per group) were injected with clodronate liposomes 48 and 2 hours prior to the freeze injury of the left tibialis anterior (TA) muscle and every third day during the post-injury period. Control mice received phosphate buffered saline (PBS) liposomes. At 1, 3 or 9 days post-injury, the TA muscles were harvested for histology or gene expression evaluation by quantitative real time RT-PCR. Histopathological examination revealed less inflammatory cell infiltration in the injured muscles of clodronate treated mice at day 3 post-injury and delayed muscle tissue recovery with an impaired clearance of the necrotic myofibers at day 9 post-injury. Furthermore, macrophage depletion significantly attenuated injury-induced inflammatory cytokine and growth factor mRNA expression, for example tumor necrosis factor á, when compared to the PBS-liposome treated mice. These findings define the role of macrophages and the related cytokines as critical components of the complete recovery from skeletal muscle traumatic injury.
Skeletal-system; Skeletal-system-disorders; Musculoskeletal-system; Musculoskeletal-system-disorders; Animal-studies; Laboratory-animals; Histopathology; Cell-function; Muscle-function; Muscle-cells
Abstract; Conference/Symposia Proceedings
The FASEB Journal, Immunology 2003, Denver, Colorado May 6-10, 2003