Human macrophages rescue myoblasts and myotubes from apoptosis through a set of adhesion molecular systems.
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.
Sonnet
Corinne
C
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.
Lafuste
Peggy
P
Arnold
Ludovic
L
Brigitte
Madly
M
Poron
Françoise
F
Authier
Françoise-Jérôme
FJ
Chrétien
Fabrice
F
Gherardi
Romain K
RK
Chazaud
Bénédicte
B
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004546:Elapid Venoms / Q000008:administration & dosage; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D032342:Muscle Cells / Q000166:cytology / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000293:injuries; D032446:Myoblasts / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D015815:Cell Adhesion Molecules; D004546:Elapid Venoms; C005082:notexin