Hepatocyte Growth Factor Is a Regulator of Monocyte-Macrophage Function1

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-1β 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.

[1]  Youhua Liu.  Hepatocyte growth factor promotes renal epithelial cell survival by dual mechanisms. , 1999, American journal of physiology. Renal physiology.

[2]  P. Schirmacher,et al.  Neoexpression of the c-met/hepatocyte growth factor-scatter factor receptor gene in activated monocytes. , 1997, Blood.

[3]  T. Evans,et al.  Developmental biology of hematopoiesis. , 1997, Hematology/oncology clinics of North America.

[4]  F. Blasi.  uPA, uPAR, PAI-1: key intersection of proteolytic, adhesive and chemotactic highways? , 1997, Immunology today.

[5]  Q. Chen,et al.  Induction of met proto-oncogene (hepatocyte growth factor receptor) expression during human monocyte-macrophage differentiation. , 1996, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[6]  A. Ullrich,et al.  Rapid and Long Term Effects of Protein Kinase C on Receptor Tyrosine Kinase Phosphorylation and Degradation (*) , 1995, The Journal of Biological Chemistry.

[7]  G. Michalopoulos,et al.  The many faces of hepatocyte growth factor: from hepatopoiesis to hematopoiesis , 1995, The Journal of cell biology.

[8]  A. Bardelli,et al.  Biological Activation of pro-HGF (Hepatocyte Growth Factor) by Urokinase Is Controlled by a Stoichiometric Reaction (*) , 1995, The Journal of Biological Chemistry.

[9]  F. Galimi,et al.  Hepatocyte growth factor induces proliferation and differentiation of multipotent and erythroid hemopoietic progenitors , 1994, The Journal of cell biology.

[10]  F. Galimi,et al.  Hepatocyte growth factor (HGF) receptor expression is inducible and is part of the delayed-early response to HGF. , 1994, The Journal of biological chemistry.

[11]  S. Giordano,et al.  Structure and inducible regulation of the human MET promoter. , 1994, The Journal of biological chemistry.

[12]  A. Bardelli,et al.  A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family , 1994, Cell.

[13]  K. Matsumoto,et al.  Hepatocyte growth factor specifically binds to sulfoglycolipids. , 1994, The Journal of biological chemistry.

[14]  L. McManus,et al.  PAF molecular heterogeneity: pathobiological implications. , 1993, Laboratory investigation; a journal of technical methods and pathology.

[15]  C. Birchmeier,et al.  Scatter factor/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development , 1993, The Journal of cell biology.

[16]  H. Koyama,et al.  Regulation of release of hepatocyte growth factor from human promyelocytic leukemia cells, HL-60, by 1,25-dihydroxyvitamin D3, 12-O-tetradecanoylphorbol 13-acetate, and dibutyryl cyclic adenosine monophosphate. , 1993, Blood.

[17]  P. Comoglio,et al.  Hepatocyte growth factor/scatter factor stimulates the Ras-guanine nucleotide exchanger. , 1993, The Journal of biological chemistry.

[18]  H. Kleinman,et al.  Scatter factor induces blood vessel formation in vivo. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[19]  E Medico,et al.  Transfer of motogenic and invasive response to scatter factor/hepatocyte growth factor by transfection of human MET protooncogene. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[20]  W. Birchmeier,et al.  Extracellular proteolytic cleavage by urokinase is required for activation of hepatocyte growth factor/scatter factor. , 1992, The EMBO journal.

[21]  L. Naldini,et al.  Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth , 1992, The Journal of cell biology.

[22]  K. Miyazawa,et al.  Activation of hepatocyte growth factor by proteolytic conversion of a single chain form to a heterodimer. , 1992, The Journal of biological chemistry.

[23]  A. Bardelli,et al.  Autophosphorylation promotes complex formation of recombinant hepatocyte growth factor receptor with cytoplasmic effectors containing SH2 domains. , 1992, Oncogene.

[24]  P. Godowski,et al.  Structure‐function analysis of hepatocyte growth factor: identification of variants that lack mitogenic activity yet retain high affinity receptor binding. , 1992, The EMBO journal.

[25]  P. Comoglio,et al.  C-terminal truncated forms of Met, the hepatocyte growth factor receptor , 1991, Molecular and cellular biology.

[26]  L. Orci,et al.  Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor , 1991, Cell.

[27]  L. Cantley,et al.  The tyrosine-phosphorylated hepatocyte growth factor/scatter factor receptor associates with phosphatidylinositol 3-kinase. , 1991, The Journal of biological chemistry.

[28]  A. Bardelli,et al.  Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor. , 1991, The EMBO journal.

[29]  P. Comoglio,et al.  The receptor encoded by the human C‐MET oncogene is expressed in hepatocytes, epithelial cells and solid tumors , 1991, International journal of cancer.

[30]  W. Birchmeier,et al.  Evidence for the identity of human scatter factor and human hepatocyte growth factor. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[31]  T. Nakamura,et al.  Identification and change in the receptor for hepatocyte growth factor in rat liver after partial hepatectomy or induced hepatitis. , 1991, Biochemical and biophysical research communications.

[32]  P. Comoglio,et al.  c-met is amplified but not mutated in a cell line with an activated met tyrosine kinase. , 1991, Oncogene.

[33]  G. Michalopoulos,et al.  Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET. , 1991, Oncogene.

[34]  J Vandekerckhove,et al.  Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells , 1990, The Journal of cell biology.

[35]  K. Tashiro,et al.  Molecular cloning and expression of human hepatocyte growth factor , 1989, Nature.

[36]  C. Cooper,et al.  Biosynthesis of the protein encoded by the c-met proto-oncogene. , 1989, Oncogene.

[37]  J. Enghild,et al.  NH2-terminal amino acid sequence of rabbit hepatopoietin A, a heparin-binding polypeptide growth factor for hepatocytes. , 1989, Biochemical and biophysical research communications.

[38]  C. Cooper,et al.  Tyrosine kinase receptor indistinguishable from the c-met protein , 1989, Nature.

[39]  A. Mantovani,et al.  Granulocyte- and granulocyte– macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate , 1989, Nature.

[40]  M. Stratton,et al.  Structure of the met protein and variation of met protein kinase activity among human tumour cell lines. , 1988, British Journal of Cancer.

[41]  C. Dinarello,et al.  Interleukin-1 stimulates diacylglycerol production in T lymphocytes by a novel mechanism , 1988, Cell.

[42]  Michael Stoker,et al.  Scatter factor is a fibroblast-derived modulator of epithelial cell mobility , 1987, Nature.

[43]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[44]  G. Michalopoulos,et al.  Control of hepatocyte replication by two serum factors. , 1984, Cancer research.

[45]  D. Belin,et al.  Concomitant secretion of prourokinase and of a plasminogen activator- specific inhibitor by cultured human monocytes-macrophages , 1984, The Journal of experimental medicine.

[46]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[47]  J. Bousquet,et al.  Updates on cells and cytokines : monocytes , 1998 .

[48]  T. Suzuki,et al.  Lipopolysaccharide receptors and signal transduction pathways in mononuclear phagocytes. , 1992, Current topics in microbiology and immunology.

[49]  A. Mantovani,et al.  Interaction between fibrinogen and cultured endothelial cells. Induction of migration and specific binding. , 1985, The Journal of clinical investigation.