title: Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct binding to CD160 receptor expressed by endothelial cells.
abstract: HLA-G is a major histocompatibility complex class Ib molecule whose constitutive tissue distribution is restricted mainly to trophoblast cells at the maternal-fetal interface during pregnancy. In this study, we demonstrated the ability of the soluble HLA-G1 (sHLA-G1) isoform to inhibit fibroblast growth factor-2 (FGF2)-induced capillary-like tubule formation. Using a rabbit corneal neovascularization model, we further showed that sHLA-G1 inhibits FGF2-induced angiogenesis in vivo. We also demonstrated that sHLA-G1 induces endothelial cell apoptosis through binding to BY55/CD160, a glycosylphosphatidylinositolanchored receptor expressed by endothelial cells. Furthermore, we showed that the specific CL1-R2 anti-CD160 monoclonal antibody mimics sHLA-G1-mediated inhibition of endothelial cell tube formation and induction of apoptosis. Thus, the engagement of CD160 in endothelial cells may be essential for the inhibition of angiogenesis. sHLA-G1/CD160-mediated antiangiogenic property may participate in the vascular remodeling of maternal spiral arteries during pregnancy, and, given that we found that CD160 is strongly expressed in the vasculature of a murine tumor, it offers an attractive therapeutic target for preventing pathologic neovascularization.
authors.affiliation: Institut de Pharmacologie et Biologie Structurale, Centre National de la Recherche Scientifique, UMR 5089, INSERM U563, Bât A, Hopital Purpan, BP3028, 31024 Toulouse Cedex 3, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fons
authors.forename: Sophie
authors.initials: S
authors.lastname: Chabot
authors.forename: Judith E
authors.initials: JE
authors.lastname: Cartwright
authors.forename: Francoise
authors.initials: F
authors.lastname: Lenfant
authors.forename: Fatima
authors.initials: F
authors.lastname: L'Faqihi
authors.forename: Jerome
authors.initials: J
authors.lastname: Giustiniani
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: Herault
authors.forename: Genevieve
authors.initials: G
authors.lastname: Gueguen
authors.forename: Françoise
authors.initials: F
authors.lastname: Bono
authors.forename: Pierre
authors.initials: P
authors.lastname: Savi
authors.forename: Maryse
authors.initials: M
authors.lastname: Aguerre-Girr
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fournel
authors.forename: François
authors.initials: F
authors.lastname: Malecaze
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.forename: Jean
authors.initials: J
authors.lastname: Plouët
authors.forename: Philippe
authors.initials: P
authors.lastname: Le Bouteiller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D002478:Cells, Cultured; D003315:Cornea / Q000098:blood supply / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D058851:GPI-Linked Proteins; D006680:HLA Antigens / Q000378:metabolism* / Q000494:pharmacology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011817:Rabbits; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D012995:Solubility
chemical_list: D015703:Antigens, CD; C114505:CD160 protein, human; C511585:Cd160 protein, mouse; D058851:GPI-Linked Proteins; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D011971:Receptors, Immunologic; D016222:Fibroblast Growth Factor 2