title: Anti-HLA antibodies can induce endothelial cell survival or proliferation depending on their concentration.
abstract: Patients exhibiting a humoral immune response to the transplanted organ are at increased risk of antibody-mediated rejection and development of transplant vasculopathy. Historically, antibodies were thought to elicit transplant rejection through complement mediated damage of the endothelium of the graft. More recently, studies from our laboratory and others have shown that antibody ligation of class I molecules on the surface of endothelial cells transduces signals resulting in functional changes including expression of cell survival proteins and cell proliferation. The intracellular events initiated by antibody ligation are dependent upon the degree of molecular aggregation and influenced by the concentration of the antibody and level of human leukocyte antigen (HLA) expression. Herein we describe our recent findings on the effect of molecular aggregation on the class I signaling pathway in human endothelial cells.
authors.affiliation: Department of Pathology and Laboratory Medicine, UCLA Immunogenetics Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Jindra
authors.forename: Xiaohai
authors.initials: X
authors.lastname: Zhang
authors.forename: Arend
authors.initials: A
authors.lastname: Mulder
authors.forename: Frans
authors.initials: F
authors.lastname: Claas
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Veale
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Jin
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Reed
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology; D006680:HLA Antigens / Q000032:analysis / Q000276:immunology*; D006801:Humans
chemical_list: D000911:Antibodies, Monoclonal; D006680:HLA Antigens