Neutrophils Contribute To Muscle Injury And Impair Its Resolution After Lengthening Contractions In Mice

Abstract

PURPOSE To test the hypotheses that: 1) neutrophil accumulation after contraction-induced muscle injury is dependent on the β2 integrin CD18, 2) neutrophils contribute to muscle injury and oxidative damage after contraction-induced muscle injury, and 3) neutrophils aid the resolution of contraction-induced muscle injury. METHODS The extensor digitorum longus (EDL) muscles of mice deficient in CD18 (CD18−/−; Itgb2tmlBay) and of wild type mice (C57BL/6) were exposed to in situ lengthening contractions. Markers of muscle inflammation, injury, oxidative damage, and regeneration were quantified. RESULTS Neutrophil concentrations were significantly elevated in wild type mice at 6 h and 3 d post lengthening contractions; however neutrophils remained at control levels at these time points in CD18−/− mice. These data indicate that CD18 is required for neutrophil accumulation after contraction-induced muscle injury. Histological and functional signs of muscle injury and total carbonyl content, a marker of oxidative damage, were significantly higher in wild type relative to CD 18−/− mice 3 d after lengthening contractions. These data show that neutrophils exacerbate contraction-induced muscle injury. Wild type mice also demonstrated a higher functional deficit at 7 d, a lower percentage of myofibers expressing embryonic myosin heavy chain at 3 and 7 d, and a smaller cross sectional area of central nucleated myofibers at 14 d relative to CD18−/− mice. These observations suggest that neutrophils impair the restoration of muscle structure and function after injury. CONCLUSIONS Neutrophil accumulation after contraction-induced muscle injury is dependent on CD18. Furthermore, neutrophils appear to contribute to muscle injury and impair some of the events associated with the resolution of contraction-induced muscle injury. Supported by NIH Grant RO3 AR47599 and an award from the AHA, Ohio Valley Affiliate.