IMMUNOLOCALIZATION OF FGF-1 AND RECEPTORS IN HUMAN RENAL-ALLOGRAFT VASCULOPATHY ASSOCIATED WITH CHRONIC REJECTION

Despite recognition of chronic vasculo-occlusive disease in solid orga n transplantation, the exact pathophysiologic events resulting in neoi ntima formation remain to be elucidated. Since acidic fibroblast growt h factor (FGF-1) is an established modulator of vascular cell function , we examined the expression of this growth factor and its high affini ty receptors in both relevant renal transplant controls (n=5) and tiss ue from patients (n=19) who underwent nephrectomy following graft loss secondary to chronic rejection. In situ hybridization and immunohisto chemical studies demonstrated minimal vascular expression and distribu tion of FGF-1 and FGF high affinity receptors in the normal human kidn ey. In contrast, vascular lesions in kidney allografts experiencing ch ronic rejection demonstrated the exaggerated appearance of FGF-1 ligan d and receptors. Immunoreactive FGF-1 readily was detected in medial s mooth muscle cells and focal areas of intimal hyperplasia, particularl y in association with the presence of inflammatory infiltrate. Enhance d staining for FGF-1 mRNA primarily was associated with the appearance of resident inflammatory cells. Medial smooth muscle cells of hyperpl astic vascular structures demonstrated the greatest immunoappearance o f FGF receptors-however, diffuse immunostaining also was observed in a reas of intimal hyperplasia. The enhanced appearance of both FGF-1 and FGF receptors in the vascular wall suggests that this polypeptide mit ogen may serve as an important mediator of growth responses associated with neointima development and angiogenesis during chronic rejection of human renal allografts.