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
H. Bian et al., 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, International immunology (Print), 10(9), 1998, pp. 1315-1323
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.