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Am J Physiol Cell Physiol 288: C721-C729, 2005. First published November 17, 2004; doi:10.1152/ajpcell.00237.2004
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MUSCLE CELL BIOLOGY AND CELL MOTILITY

Mechanical loading and injury induce human myotubes to release neutrophil chemoattractants

Susan K. Tsivitse ,1,* Eleni Mylona,1,* Jennifer M. Peterson,1 William T. Gunning,2 and Francis X. Pizza1

1Department of Kinesiology, University of Toledo, and 2Department of Pathology, Medical College of Ohio, Toledo, Ohio

Submitted 12 May 2004 ; accepted in final form 11 November 2004

The purpose of this study was to 1) test the hypothesis that skeletal muscle cells (myotubes) after mechanical loading and/or injury are a source of soluble factors that promote neutrophil chemotaxis and superoxide anion (O2·) production and 2) determine whether mechanical loading and/or injury causes myotubes to release cytokines that are known to influence neutrophil responses [tumor necrosis factor-{alpha} (TNF-{alpha}), IL-8, and transforming growth factor-{beta}1 (TGF-{beta}1)]. Human myotubes were grown in culture and exposed to either a cyclic strain (0, 5, 10, 20, or 30% strain) or a scrape injury protocol. Protocols of 5, 10, and 20% strain did not cause injury, whereas 30% strain and scrape injury caused a modest and a high degree of injury, respectively. Conditioned media from strained myotubes promoted chemotaxis of human blood neutrophils and primed them for O2· production in a manner that was dependent on a threshold of strain and independent from injury. Neutrophil chemotaxis, but not priming, progressively increased with higher magnitudes of strain. Conditioned media only from scrape-injured myotubes increased O2· production from neutrophils. Concentrations of IL-8 and total TGF-{beta}1 in conditioned media were reduced by mechanical loading, whereas TNF-{alpha} and active TGF-{beta}1 concentrations were unaffected. In conclusion, skeletal muscle cells after mechanical loading and injury are an important source of soluble factors that differentially influence neutrophil chemotaxis and the stages of neutrophil-derived reactive oxygen species production. Neutrophil responses elicited by mechanical loading, however, did not parallel changes in the release of IL-8, TGF-{beta}1, or TNF-{alpha} from skeletal muscle cells.

inflammation; cytokines; exercise; free radicals



Address for reprint requests and other correspondence: F. X. Pizza, Dept. of Kinesiology, Univ. of Toledo, 2801 W. Bancroft St., Toledo, OH 43606 (E-mail: Francis.Pizza{at}utoledo.edu)




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