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This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/R1831    most recent 90318.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dumont, N. Articles by Frenette, J. Search for Related Content PubMed PubMed Citation Articles by Dumont, N. Articles by Frenette, J.

INFLAMMATION, CYTOKINES, NEUROIMMUNE INTERACTIONS

Neutrophil-induced skeletal muscle damage: a calculated and controlled response following hindlimb unloading and reloading

¹Centre Hospitalier Universitaire de Québec-Centre de Recherche du Centre Hospitalier de l'Université Laval, Université Laval, Quebec City, Quebec, Canada; and ²Département de Réadaptation, Faculté de Médecine, Université Laval, Quebec City, Quebec, Canada

Submitted 28 March 2008 ; accepted in final form 2 September 2008

Neutrophils phagocyte necrotic debris and release cytokines, enzymes, and oxidative factors. In the present study, we investigated the contribution of neutrophils to muscle injury, dysfunction, and recovery using an unloading and reloading model. Mice were submitted to 10 days of hindlimb unloading and were transiently depleted in neutrophils with anti-Ly6G/Ly6C antibody prior to reloading. Leukocyte accumulation and muscle function were assessed immunohistologically and functionally in vitro. In addition, soleus muscles submitted to unloading and reloading were incubated in vitro with LPS (100 µg/ml) to determine whether exogenous stimulus would activate neutrophil response and produce extensive muscle damage. Contractile properties were recorded every hour for 6 h, and muscles were subsequently incubated in procion orange to assess muscle damage. Neutrophil depletion affected neither the loss in muscle force nor the time of recovery in atrophied and reloaded soleus muscles. However, atrophied and reloaded soleus muscles that contained high concentration of neutrophils experienced a 20% greater loss in force than atrophied and reloaded soleus muscles depleted in neutrophils following in vitro incubation with LPS. Procion orange dye also confirmed that neutrophils induced a 2.5-fold increase in muscle membrane damage in the presence of LPS. These results show that neutrophil infiltration during modified mechanical loading is highly regulated and efficiently eliminated, with no significant muscle fiber injury unless the activation state of neutrophils is modified by the presence of LPS.

neutrophils; hindlimb suspension; contractile properties; inflammation