Neutrophils contribute to muscle injury and impair its resolution after lengthening contractions in mice.
We tested the hypotheses that: (1) neutrophil accumulation after contraction-induced muscle injury is dependent on the beta(2) 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(-/-); Itgb2(tm1Bay)) 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.
Pizza
Francis X
FX
Dept of Kinesiology, The University of Toledo, 2801 W. Bancroft Street, Toledo, OH 43606, USA. francis.pizza@utoledo.edu
Peterson
Jennifer M
JM
Baas
Joel H
JH
Koh
Timothy J
TJ
D000818:Animals; D018821:CD18 Antigens / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000276:immunology*; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000293:injuries / Q000473:pathology* / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000473:pathology / Q000503:physiopathology*; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology*; D020127:Recovery of Function / Q000276:immunology
D018821:CD18 Antigens; D009124:Muscle Proteins