Macrophage invasion does not contribute to muscle membrane injury during inflammation

Previous observations have shown that neutrophil invasion precedes macropha ge invasion during muscle inflammation and that peak muscle injury is obser ved at the peak of ED1(+) macrophage invasion. We tested the hypothesis tha t neutrophil invasion causes subsequent invasion by ED1+ macrophages and th at ED1(+) macrophages then contribute significantly to muscle membrane inju ry during modified muscle use. Rat hindlimbs were unloaded for 10 days foll owed by reloading by normal ambulation to induce inflammation. Membrane inj ury was measured Ly assaying Evans blue-bound serum protein influx through membrane lesions. Muscle neutrophil populations increased significantly dur ing the first 2 h of reloading but ED1(+) macrophages did not increase unti l 24 h. Neutrophil invasion was uncoupled from subsequent macrophage invasi on by reloading rat hindlimbs for 2 h to cause neutrophil invasion, followe d Ly resuspension for hours 2-24. This produced similar increases in neutro phil concentration as measured in muscles continuously reloaded for 24 h wi thout causing an increase in macrophages. However, resuspension did not red uce the extent of muscle damage compared with that occurring in muscles tha t were reloaded continuously for 24 h. Thus, muscle invasion by neutrophils is not sufficient to cause invasion by ED1+ macrophages. in addition, musc le membrane injury that occurs during reloading is independent of invasion by ED1+ macrophages.