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1 The University of Toledo, Department of Kinesiology, Toledo, OH 43606, USA
2 University of Illinois, Chicago, School of Kinesiology, Chicago, IL 60608, USA
We tested the hypotheses that: (1) neutrophil accumulation after contraction-induced muscle injury is dependent on the ß2 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. These hypotheses were tested by exposing extensor digitorum longus (EDL) muscles of mice deficient in CD18 (CD18–/–; Itgb2tm1Bay) and of wild type mice (C57BL/6) to in situ lengthening contractions and by quantifying markers of muscle inflammation, injury, oxidative damage and regeneration/repair. Neutrophil concentrations were significantly elevated in wild type mice at 6 h and 3 days 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 (isometric force deficit) signs of muscle injury and total carbonyl content, a marker of oxidative damage, were significantly higher in wild type relative to CD18–/– mice 3 days after lengthening contractions. These data show that neutrophils exacerbate contraction-induced muscle injury. After statistically controlling for differences in the force deficit at 3 days, wild type mice also demonstrated a higher force deficit at 7 days, a lower percentage of myofibres expressing embryonic myosin heavy chain at 3 and 7 days, and a smaller cross sectional area of central nucleated myofibres at 14 days relative to CD18–/– mice. These observations suggest that neutrophils impair the restoration of muscle structure and function after injury. In conclusion, 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.
(Received 16 August 2004;
accepted after revision 11 November 2004;
first published online 18 November 2004)
Corresponding author F. X. Pizza: Dept of Kinesiology, The University of Toledo, 2801 W. Bancroft Street, Toledo, OH 43606, USA. Email: francis.pizza{at}utoledo.edu
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