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Deferoxamine reduces and nitric oxide synthase inhibition increases neutrophil-mediated myotube injury

Abstract

We tested the contribution of reactive oxygen species (ROS), reactive nitrogen species (RNS) and the β2 integrin CD18 to neutrophil-mediated myotube injury. Human myotubes were cultured with human neutrophils in the presence or absence of inhibitors directed against ROS, RNS, and CD18. Muscle injury was assessed by a 51Cr release assay. The inclusion of superoxide dismutase (50–500 U/ml) in the culture medium did not affect myotube injury. A significant protective effect was provided by including catalase (600–2400 U/ml), deferoxamine (1–2 mM), or anti-CD18 antibody (10 μg/ml) in the culture medium. S-Ethylisothiourea (500–1000 μM), an inhibitor of nitric oxide synthase (NOS), significantly increased myotube injury and reduced nitric oxide (NO) in cultures consisting of only myotubes. In conclusion, neutrophil-mediated skeletal muscle injury appears to be largely dependent on CD18-mediated neutrophil adhesion and iron-dependent hydroxyl radical production. In addition, skeletal muscle NOS activity may protect skeletal muscle against the injury caused by neutrophils.

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Acknowledgements

The authors thank Dr. Scott Boitano (University of Arizona, Tucson) for his assistance in the measurement of nitric oxide in our cultures and Drs. Charles Creutz, Alice McAfee and P. Gunnar Brolinson for their insight throughout the project.

Author information

Correspondence to Francis X. Pizza.

Additional information

This project was supported by The University of Toledo DeArce Memorial Fund and the National Institutes of Health AR47599-01

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McLoughlin, T.J., Tsivitse, S.K., Edwards, J.A. et al. Deferoxamine reduces and nitric oxide synthase inhibition increases neutrophil-mediated myotube injury. Cell Tissue Res 313, 313–319 (2003). https://doi.org/10.1007/s00441-003-0767-4

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Keywords

  • Skeletal muscle
  • Injury
  • Reactive oxygen species
  • Reactive nitrogen species
  • Human