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Hepatocyte Growth Factor Is a Regulator of Monocyte-Macrophage Function¹

Francesco Galimi^2,*, Erika Cottone, Elisa Vigna, Nicolò Arena^*, Carla Boccaccio, Silvia Giordano, Luigi Naldini and Paolo M. Comoglio

^* Department of Biomedical Sciences, University of Sassari Medical School, Sassari, Italy and Institute for Cancer Research, University of Turin Medical School, Turin, Italy

Hepatocyte growth factor (HGF) is a potent paracrine mediator of stromal/epithelial interactions, which is secreted as a matrix-associated inactive precursor (pro-HGF) and locally activated by tightly controlled urokinase cleavage. It induces proliferation and motility in epithelial and endothelial cells, and plays a role in physiological and pathological processes involving invasive cell growth, such as angiogenesis and parenchymal regeneration. We now report that HGF induces directional migration and cytokine secretion in human monocytes. Monocyte activation by endotoxin and IL-1 results in the up-regulation of the HGF receptor expression and in the induction of cell-associated pro-HGF convertase activity, thus enhancing cell responsiveness to the factor. Furthermore, we provide evidence for the secretion of biologically active HGF by activated monocytes, implying an autocrine stimulation. Altogether, these data indicate that monocyte function is modulated by HGF in a paracrine/autocrine manner, and provide a new link between stromal environment and mononuclear phagocytes.

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