Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct binding to CD160 receptor expressed by endothelial cells.
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.
Fons
Pierre
P
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.
Chabot
Sophie
S
Cartwright
Judith E
JE
Lenfant
Francoise
F
L'Faqihi
Fatima
F
Giustiniani
Jerome
J
Herault
Jean-Pascal
JP
Gueguen
Genevieve
G
Bono
Françoise
F
Savi
Pierre
P
Aguerre-Girr
Maryse
M
Fournel
Sylvie
S
Malecaze
François
F
Bensussan
Armand
A
Plouët
Jean
J
Le Bouteiller
Philippe
P
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
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