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 chro nic rejection, is the major obstacle to long-term survival of cardiac and renal allografts. The incidence of transplant atherosclerosis is i ncreased in transplant recipients producing antidonor HLA antibodies f ollowing transplantation, suggesting that anti-H LA antibodies play a role in the pathogenesis of the disease. We have postulated that anti- HLA antibodies mediate the development of transplant atherosclerosis b y 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 transd uce signals in smooth muscle cells stimulating increased tyrosine phos phorylation of intracellular proteins and up-regulation of fibroblast growth factor (FGF) receptors. Antibody binding to class I molecules o n smooth muscle cells is also accompanied by increased responsiveness to basic FGF and augmented cell proliferation. These findings may expl ain the increased occurrence of transplant atherosclerosis in recipien ts producing anti-donor HLA antibodies.