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Monocyte depletion increases local proliferation of macrophage subsets after skeletal muscle injury

Côté Claude H., Bouchard Patrice, van Rooijen Nico, Marsolais David et Duchesne Élise. (2013). Monocyte depletion increases local proliferation of macrophage subsets after skeletal muscle injury. BMC Musculoskeletal Disorders, 14, p. 359.

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Background : Sequential accumulation of M1 and M2 macrophages is critical for skeletal muscle recovery after an acute injury. While M1 accumulation is believed to rely on monocyte infiltration, the mechanisms of M2 accumulation remain controversial, but could involve an infiltrating precursor. Yet, strong depletion of monocytes only partiallt impairs skeletal muscle healing, supporting the existence of alternative mechanisms to palliate the loss of infiltrating macrophage progenitors. The aims of this study are thus to investigate if proliferation occurs in macrophage subsets within injured skeletal muscles; and to determine if monocyte depletion leads to increased proliferation of macrophages after injury.

Methods : Injury was induced by bupivacaine injection in the tibialis anterior muscle of rats. Blood monocytes were depleted by daily intravenous injections of liposome-encapsulated clodronate, starting 24 h prior to injury. In separate experiments, irradiation of hind limb was also performed to prevent resident cell proliferation. Upon euthanasia, blood and muscles were collected for flow cytometric analyses of macrophage/monocyte subsets.

Results : Clodronate induced a 80%-90% depletion of monocyte but only led to 57% and 41% decrease of M1 and M2 macrophage accumulation, respectively, 2 d following injury. Conversely, the number of M1 macrophages in monocyte-depleted rats was 2.4-fold higher than in non-depleted rats 4 d after injury. This was associated with a 16-fold increase in the number of proliferative M1 macrophages, which was reduced by 46% in irradiated animals. Proliferation of M2 macrophages was increased tenfold by clodronate treatment 4 d post injury. The accumulation of M2 macrophages was partially impaired by irradiation, regardless of monocyte depletion.

Conclusions : M1 and M2 subsets proliferate after skeletal muscle injury and their proliferation is enhanced under condition of monocyte depletion. Our study supports the conclusion that both infiltrating and resident precursors could contribute to M1 or M2 macrophage accumulation in muscle injury.

Type de document:Article publié dans une revue avec comité d'évaluation
Pages:p. 359
Version évaluée par les pairs:Oui
Sujets:Sciences de la santé
Sciences de la santé > Sciences de l'activité physique et réadaptation
Sciences de la santé > Sciences de l'activité physique et réadaptation > Physiothérapie
Département, module, service et unité de recherche:Départements et modules > Département des sciences de la santé > Unité d'enseignement en physiothérapie
Mots-clés:M1, M2, bupivacaine, clodronate, flow cytometrym ED1, ED2, Ki67, irradiation, healing
Déposé le:21 sept. 2016 14:39
Dernière modification:07 mars 2018 02:37
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