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Related Collections Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 April 2002, Vol. 99, No. 8, pp. 2997-3004 PHAGOCYTES Presence of a mobilizable intracellular pool of hepatocyte growth factor in human polymorphonuclear neutrophils Alain Grenier, Sylvie Chollet-Martin, Bruno Crestani, Charlotte Delarche, Jamel El Benna, Anne Boutten, Valérie Andrieu, Geneviève Durand, Marie-Anne Gougerot-Pocidalo, Michel Aubier, and Monique Dehoux From the Laboratoire de Biochimie, Hôpital de Montfermeil, Montfermeil, France; and the Laboratoire de Biochimie, INSERM U 408, Laboratoire d'Hématologie et d'Immunologie et INSERM U 479, and Service de Pneumologie, Hôpital Bichat Assistance Publique-Hôpitaux de Paris, Paris, France. Hepatocyte growth factor (HGF), a heparin-binding factor, is synthesized as a single-chain inactive precursor (pro-HGF), which is converted by proteolysis to an active heterodimer (mature HGF). HGF has pleiotropic activities and has been implicated in the regulation of mitogenesis, motogenesis, and morphogenesis of epithelial and endothelial cells. As polymorphonuclear neutrophils (PMNs) secrete numerous cytokines involved in the modulation of local inflammation, we investigated their ability to produce HGF. We found that HGF was stored in secretory vesicles and in gelatinase/specific granules. This intracellular stock was rapidly mobilized by degranulation when neutrophils were stimulated with phorbol myristate acetate or N-formylmethionyl-leucyl-phenylalanine. Cycloheximide did not affect the release of HGF. Moreover, HGF messenger RNA and protein expression was found in bone marrow myeloid cells, suggesting that HGF synthesis likely occurs during PMN maturation. In mature circulating PMNs, intracellular HGF was in the pro-HGF form, whereas the HGF secreted by degranulation was the mature form. Furthermore, PMNs pretreated with diisopropyl fluorophosphate only released the pro-HGF form, suggesting that PMN-derived serine protease(s) are involved in the proteolytic process. We also obtained evidence that secreted mature HGF binds PMN-derived glycosaminoglycans (probably heparan sulfate). These findings suggest that PMNs infiltrating damaged tissues may modulate local wound healing and repair through the production of HGF, a major mediator of tissue regeneration. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Quesnel, S. Marchand-Adam, A. Fabre, J. Marchal-Somme, I. Philip, S. Lasocki, V. Lecon, B. Crestani, and M. Dehoux Regulation of hepatocyte growth factor secretion by fibroblasts in patients with acute lung injury Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L334 - L343. [Abstract] [Full Text] [PDF] M. Bonay, A. 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