INDUCTION OF HIGH-AFFINITY FIBROBLAST GROWTH-FACTOR RECEPTOR EXPRESSION AND PROLIFERATION IN HUMAN ENDOTHELIAL-CELLS BY ANTI-HLA ANTIBODIES- A POSSIBLE MECHANISM FOR TRANSPLANT ATHEROSCLEROSIS

The major limitation to long term survival of organ allografts is chro nic rejection, which is manifested as atherosclerosis of the vessels o f the transplanted organ, There is a significant association between t ransplant atherosclerosis and the development of Abs to the disparate HLA Ags present on the graft vasculature, We have investigated the eff ect of anti-HLA Abs on endothelial cells (EC) and smooth muscle cells cultured in vitro. Ab ligation of class I molecules on ECs results in increased high affinity fibroblast growth factor receptor mRNA express ion, and enhanced basic fibroblast growth factor ligand binding. Ab bi nding to class I molecules on EC and smooth muscle cells is also accom panied by augmented cell proliferation, These results suggest that the intimal thickening observed in transplant atherosclerosis is the resu lt of the proliferative effects of anti-HLA Abs.