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First published online 23 May 2006
doi: 10.1242/jcs.02988

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Human macrophages rescue myoblasts and myotubes from apoptosis through a set of adhesion molecular systems

C. Sonnet^*, P. Lafuste^*, L. Arnold, M. Brigitte, F. Poron, F. Authier, F. Chrétien, R. K. Gherardi and B. Chazaud

INSERM E0011 `Cellular interactions in the neuromuscular system', Faculté de Médecine, Institut National de la Santé et de la Recherche Médicale; Université Paris XII, 8 rue du Général Sarrail, 94000 Créteil, France

Author for correspondence (e-mail: benedicte.chazaud{at}creteil.inserm.fr)

Accepted 22 March 2006

The mechanisms underlying stromal cell supportive functions are incompletely understood but probably implicate a mixture of cytokines, matrix components and cell adhesion molecules. Skeletal muscle uses recruited macrophages to support post-injury regeneration. We and others have previously shown that macrophages secrete mitogenic factors for myogenic cells. Here, we focused on macrophage-elicited survival signals. We demonstrated that: (1) macrophage influx is temporally correlated with the disappearance of TUNEL-positive apoptotic myogenic cells during post-injury muscle regeneration in mice; (2) direct cell-cell contacts between human macrophages and myogenic cells rescue myogenic cells from apoptosis, as assessed by decreased annexin V labelling and caspase-3 activity, and by increased DIOC-6 staining, Bcl-2 expression and phosphorylation of Akt and ERK1/2 survival pathways; (3) four pro-survival cell-cell adhesion molecular systems detected by DNA macroarray are expressed by macrophages and myogenic cells in vitro and in vivo - VCAM-1-VLA-4, ICAM-1-LFA-1, PECAM-1-PECAM-1 and CX3CL1-CX3CR1; (4) macrophages deliver anti-apoptotic signals through all four adhesion systems, as assessed by functional analyses with blocking antibodies; and (5) macrophages more strongly rescue differentiated myotubes, which must achieve adhesion-induced stabilisation of their structure to survive. Macrophages could secure these cells until they establish final association with the matrix.

Key words: Skeletal muscle, Myogenic precursor cells, Macrophage, Apoptosis, Cell adhesion molecules

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