title: Characterization of FGF receptor expression in human neutrophils and their contribution to chemotaxis.
abstract: Several members of the fibroblast growth factor (FGF) family are potent endothelial cell (EC) mitogens and angiogenic factors, and their activities can be mediated by four tyrosine kinase receptors (FGFR1-4). In addition, FGFs can induce the release of inflammatory mediators by ECs and the expression of adhesion molecules at their surface, thereby favoring the recruitment and transvascular migration of inflammatory cells such as neutrophils. Neither the expression nor the biological activities that could be mediated by FGFRs have been investigated in human neutrophils. By biochemical and cytological analyses, we observed that purified circulating human neutrophils from healthy individuals expressed varying levels of FGFRs in their cytosol and at their cytoplasmic membrane. FGFR-2 was identified as the sole cell surface receptor, with FGFR-1 and -4 localizing in the cytosol and FGFR-3 being undetectable. We assessed the capacity of FGF-1 and FGF-2 to induce neutrophil chemotaxis in a modified Boyden microchamber and observed that they increase neutrophil transmigration at 10(-10) and 10(-9) M and by 1.77- and 2.34-fold, respectively, as compared with PBS-treated cells. Treatment with a selective anti-FGFR-2 antibody reduced FGF-1-mediated chemotaxis by 75% and abrogated the effect of FGF-2, while the blockade of FGFR-1 and -4 partially inhibited (15-40%) FGF-chemotactic activities. In summary, our data are the first to report the expression of FGF receptors in human neutrophils, with FGF-1 and FGF-2 promoting neutrophil chemotaxis mainly through FGFR-2 activation.
authors.affiliation: Research Center, Montreal Heart Institute, Montreal, Quebec, Canada.
authors.forename: Lydia E
authors.initials: LE
authors.lastname: Haddad
authors.forename: Lara Bou
authors.initials: LB
authors.lastname: Khzam
authors.forename: Fadi
authors.initials: F
authors.lastname: Hajjar
authors.forename: Yahye
authors.initials: Y
authors.lastname: Merhi
authors.forename: Martin G
authors.initials: MG
authors.lastname: Sirois
mesh_terms: D002634:Chemotaxis, Leukocyte; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000378:metabolism; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; C496365:FGFR3 protein, human; C496371:FGFR4 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3; D051499:Receptor, Fibroblast Growth Factor, Type 4