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Complement activation promotes muscle inflammation during modified muscle use.

J Frenette1, B Cai, J G Tidball

  • 1Departments of Physiological Science and Pathology and Laboratory Medicine, University of California, Los Angeles 90095-1527, USA.

The American Journal of Pathology
|June 15, 2000
PubMed
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The complement system, crucial for immune responses, is activated during muscle reloading after disuse, contributing to inflammation. Inhibiting this system reduces inflammatory cell infiltration and edema in reloading muscles.

Area of Science:

  • Muscle physiology
  • Immunology
  • Inflammation research

Background:

  • Modified muscle use, such as disuse and subsequent reloading, can lead to muscle inflammation.
  • The specific triggers and early cellular mechanisms driving this inflammation remain incompletely understood.

Purpose of the Study:

  • To investigate the role of the complement system in muscle inflammation following altered loading conditions.
  • To determine if complement activation contributes to inflammatory cell recruitment and edema during muscle reloading.

Main Methods:

  • Rats underwent hindlimb unloading for 10 days, followed by reloading.
  • The complement inhibitor soluble complement receptor 1 (sCR1) was administered.
  • Complement activation pathways (classical and alternative) were assessed via C4 and factor B levels.
Keywords:
NASA Discipline MusculoskeletalNASA Program Fundamental Space BiologyNon-NASA Center

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  • Inflammatory cell infiltration (neutrophils, macrophages) and edema were quantified.

    • Main Results:

    • Muscle reloading activated both the classical and alternative complement pathways.
    • sCR1 administration significantly reduced complement activation.
    • sCR1 treatment markedly attenuated neutrophil and macrophage infiltration into muscles.
    • Edema formation was significantly reduced in sCR1-treated animals.

    Conclusions:

    • The complement system is activated during the early phase of muscle reloading after disuse.
    • Complement activation contributes to the inflammatory response, including inflammatory cell recruitment and edema.
    • Targeting the complement system may offer a therapeutic strategy for managing muscle inflammation due to altered loading.