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Published 8 December 2003. doi:10.1083/jcb.200212046
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© The Rockefeller University Press, 0021-9525/2003/12/1133 $8.00
The Journal of Cell Biology, Volume 163, Number 5, 1133-1143

Article

Satellite cells attract monocytes and use macrophages as a support to escape apoptosis and enhance muscle growth



Bénédicte Chazaud, Corinne Sonnet, Peggy Lafuste, Guillaume Bassez, Anne-Cécile Rimaniol, Françoise Poron, François-Jérôme Authier, Patrick A. Dreyfus and Romain K. Gherardi

Institut National de la Santé et de la Recherche Médicale, EMI 00-11, Université Paris XII, 94000 Créteil, France

Address correspondence to Bénédicte Chazaud, Institut National de la Santé et de la Recherche Médicale, EMI 00-11, Faculté de Médecine, 8 rue du Général Sarrail, 94000 Créteil, France. Tel.: (33) 1-49-81-36-49. Fax: (33) 1-49-81-36-42. email: benedicte.chazaud{at}creteil.inserm.fr

Once escaped from the quiescence niche, precursor cells interact with stromal components that support their survival, proliferation, and differentiation. We examined interplays between human myogenic precursor cells (mpc) and monocyte/macrophages (MP), the main stromal cell type observed at site of muscle regeneration. mpc selectively and specifically attracted monocytes in vitro after their release from quiescence, chemotaxis declining with differentiation. A DNA macroarray–based strategy identified five chemotactic factors accounting for 77% of chemotaxis: MP-derived chemokine, monocyte chemoattractant protein-1, fractalkine, VEGF, and the urokinase system. MP showed lower constitutive chemotactic activity than mpc, but attracted monocytes much strongly than mpc upon cross-stimulation, suggesting mpc-induced and predominantly MP-supported amplification of monocyte recruitment. Determination of [3H]thymidine incorporation, oligosomal DNA levels and annexin-V binding showed that MP stimulate mpc proliferation by soluble factors, and rescue mpc from apoptosis by direct contacts. We conclude that once activated, mpc, which are located close by capillaries, initiate monocyte recruitment and interplay with MP to amplify chemotaxis and enhance muscle growth.

Key Words: skeletal muscle satellite cells; stromal support; muscle regeneration; chemotaxis; myogenesis

B. Chazaud and C. Sonnet contributed equally to this work.

Anne-Cécile Rimaniol's present address is SPI-BIO, Service de Neurovirologie, CEA, Institut Paris Sud sur les Cytokines, 92260 Fontenay-aux-Roses, France.

Abbreviations used in this paper: FKN, fractalkine; HGF, hepatocyte growth factor; HMVEC, human adult microvascular endothelial cells; MCP-1, monocyte chemoattractant protein-1; MDC, MP-derived chemokine; MP, macrophages; mpc, myogenic precursor cells; PBMC, peripheral blood mononuclear cells; uPA, urokinase; uPAR, urokinase type plasminogen-activator receptor.


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