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 3 Hthymidine 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. skeletal muscle satellite cells; stromal support; muscle regeneration; chemotaxis; myogenesis Footnotes 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. Submitted: 5 December 2002 Accepted: 29 September 2003
The Journal of Cell Biology – Rockefeller University Press
Published: Dec 8, 2003
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