Hepatocyte growth factor is a regulator of monocyte-macrophage function

Hepatocyte growth factor (HGF) is a potent paracrine mediator of stromal/ep ithelial interactions, which is secreted as a matrix-associated inactive pr ecursor (pro-HGF) and locally activated by tightly controlled urokinase cle avage. It induces proliferation and motility in epithelial and endothelial cells, and plays a role in physiological and pathological processes involvi ng invasive cell growth, such as angiogenesis and parenchymal regeneration. We now report that HGF induces directional migration and cytokine secretio n in human monocytes. Monocyte activation by endotoxin and IL-1 beta result s in the up-regulation of the HGF receptor expression and in the induction of cell-associated pro-HGF convertase activity, thus enhancing cell respons iveness to the factor. Furthermore, we provide evidence for the secretion o f biologically active HGF by activated monocytes, implying an autocrine sti mulation. Altogether, these data indicate that monocyte function is modulat ed by HGF in a paracrine/autocrine manner, and provide a new link between s tromal environment and mononuclear phagocytes.