Ligation of HLA class I molecules on smooth muscle cells with anti-HLA antibodies induces tyrosine phosphorylation, fibroblast growth factor receptor expression and cell proliferation.
The development of transplant atherosclerosis, a manifestation of chronic rejection, is the major obstacle to long-term survival of cardiac and renal allografts. The incidence of transplant atherosclerosis is increased in transplant recipients producing antidonor HLA antibodies following transplantation, suggesting that anti-HLA antibodies play a role in the pathogenesis of the disease. We have postulated that anti-HLA antibodies mediate the development of transplant atherosclerosis by binding to class I molecules on the endothelium and smooth muscle of the graft and transducing signals which stimulate cell proliferation. In this report we demonstrate that anti-HLA class I antibodies transduce signals in smooth muscle cells stimulating increased tyrosine phosphorylation of intracellular proteins and up-regulation of fibroblast growth factor (FGF) receptors. Antibody binding to class I molecules on smooth muscle cells is also accompanied by increased responsiveness to basic FGF and augmented cell proliferation. These findings may explain the increased occurrence of transplant atherosclerosis in recipients producing anti-donor HLA antibodies.
Bian
H
H
Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Harris
P E
PE
Reed
E F
EF
D000906:Antibodies / Q000378:metabolism / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009124:Muscle Proteins / Q000378:metabolism*; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis*; D014180:Transplantation / Q000009:adverse effects; D014443:Tyrosine / Q000378:metabolism
D000906:Antibodies; D015395:Histocompatibility Antigens Class I; D009124:Muscle Proteins; D017468:Receptors, Fibroblast Growth Factor; D014443:Tyrosine