A macrophage-mediated factor that increases the high energy phosphate content of skeletal muscle

A marked cellular infiltrate accompanies wounding. The phagocytic and bacteriocidal activities of this infiltrate require increased substrate and O 2 consumption. This rapid utilization of available oxygen and substrates could jeopardize an already compromised resident cellular component of a wound. Recent studies have demonstrated macrophage-mediated cell stimulatory agents which induce proliferation of nonlymphoid mesenchymal cells. This study was designed to examine macrophage-resident tissue interactions and their possible significance in wounded tissue. A reconstituted wound system was designed which combines the major components of a λ-carrageenan skeletal muscle wound (muscle + macrophages). The extensor digitorum long (EDL) of male Fisher rats were incubated in a standardized fashion [12]. The groups of EDL were muscle incubated alone, muscle with the addition to the incubate of activated peritoneal macrophages or muscle with the addition of a conditioned supernatant from the incubation of activated or nonactivated peritonal macrophages. Muscle ATP and CP content were noted to be increased 46 and 22%, respectively, when macrophages and skeletal muscle were coincubated. Macrophage-conditioned media from activated or nonactivated macrophages increased the ATP and CP muscle content 44 and 37%, respectively. Preliminary characterization of this high energy phosphate (HEP) promoting factor demonstrates it to be heat and cold stable and less than 10,000 Da. Therefore, a macrophage-mediated transferable factor is capable of increasing the HEP content of skeletal muscle in an in vitro system. This may have important consequences in maintaining host cell integrity following injury.