Neoexpression of the c-met/hepatocyte growth factor-scatter factor receptor gene in activated monocytes.

Hepatocyte growth factor-scatter factor (HGF-SF ) mediates mito-, moto-, and morphogenic effects through the MET receptor, a membrane bound tyrosine kinase. HGF-SF/MET signaling is mitogenic for a large number of epithelial and endothelial cells and activates organ regeneration. HGF-SF transcripts have been detected in various myeloid cell lines. Therefore, the potential role of HGF-SF/MET signaling for circulating cells of the immune system, especially under conditions of inflammation, was evaluated. Several B-lymphoid and myeloid cell lines were found to express HGF-SF or c-met transcripts, while activity of both genes was mutually exclusive with the exception of low level coexpression in two B-cell lines. HGF-SF transcripts were present in low quantities in freshly isolated peripheral blood mononuclear cells (PBMNCs). In contrast, c-met expression was not detected in freshly isolated cells from peripheral blood, but was induced in monocytes by activation of monocytic or T-cell function. HGF-SF incubation led to an increased c-fos steady state transcript level in myeloblastic K562 cells and moderately promoted cell viability of freshly isolated preactivated monocytes. c-met expression is thus established in activated monocytes, in particular under conditions resembling inflammation, making these cells accessible to functional effects of HGF-SF.