HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 565/2/403    most recent jphysiol.2005.085506v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nguyen, H. X. Articles by Tidball, J. G. Search for Related Content PubMed PubMed Citation Articles by Nguyen, H. X. Articles by Tidball, J. G.

Departments of
¹ Physiological Science
² Medicine
³ Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA

Membrane lysis is a common and early defect in muscles experiencing acute injuries or inflammation. Although increased mechanical loading of muscles can induce inflammation and membrane lysis, whether mechanical loads applied to muscle can promote the activation and cytolytic capacity of inflammatory cells and thereby increase muscle damage is unknown. We tested whether mechanical loads applied to mouse muscle cells in vitro can increase membrane lysis, and whether neutrophil-mediated lysis of muscle cells is promoted by mechanical loads applied in vitro and in vivo. Cyclic loads applied to muscle cells for 24 h in vitro produced little muscle cell lysis. Similarly, the addition of neutrophils to muscle cell cultures in the presence of superoxide dismutase (SOD) produced little muscle cell lysis. However, when cyclic mechanical loads were applied to neutrophil–muscle co-cultures in the presence of SOD, there was a synergistic effect on muscle cell lysis, suggesting that mechanical loading activates neutrophil cytotoxicity. However, application of mechanical loads to co-cultures of muscle cells and neutrophils that are null mutants for myeloperoxidase (MPO) showed no mechanical activation of neutrophil cytotoxicity. This indicates that loading promotes neutrophil cytotoxicity via MPO. Activity assays confirmed that mechanical loading of neutrophil–muscle co-cultures significantly increased MPO activity. We further tested whether muscle membrane lysis in vivo was mediated by neutrophils when muscle was subjected to modified loading by using a mouse model of muscle reloading following a period of unloading. We observed that MPO –/– soleus muscles showed a significant 52% reduction in membrane lysis compared to wild-type mice, although the mutation did not decrease inflammatory cell extravasation. Together, these in vitro and in vivo findings show that mechanical loading activates neutrophil-mediated lysis of muscle cells through an MPO-dependent pathway.

(Received 19 February 2005; accepted after revision 19 March 2005; first published online 24 March 2005)
Corresponding author J. G. Tidball: Department of Physiological Science, 5833 Life Science Building, University of California, Los Angeles, CA 90095, USA. Email: jtidball{at}physci.ucla.edu

This article has been cited by other articles:

				N. C. Lockhart and S. V. Brooks Neutrophil accumulation following passive stretches contributes to adaptations that reduce contraction-induced skeletal muscle injury in mice J Appl Physiol, April 1, 2008; 104(4): 1109 - 1115. [Abstract] [Full Text] [PDF]

				P. K. Shireman, V. Contreras-Shannon, O. Ochoa, B. P. Karia, J. E. Michalek, and L. M. McManus MCP-1 deficiency causes altered inflammation with impaired skeletal muscle regeneration J. Leukoc. Biol., March 1, 2007; 81(3): 775 - 785. [Abstract] [Full Text] [PDF]