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

Glomerular lesions are considered one of the more detrimental patholog ic changes associated with chronic rejection of renal allografts. To e lucidate potential pathophysiologic mechanisms associated with transpl ant glomerulopathy, we examined the expression of acidic fibroblast gr owth factor (FGF-1) and its high-affinity receptors (FGFR) in both rel evant renal transplant controls (n=5) and tissue from patients (n=19) who underwent nephrectomy following graft loss secondary to chronic re jection. In situ immunohistochemical analyses demonstrated minimal sta ining and distribution of FGFR and FGF-1, which was localized to the m esangial matrix in glomeruli from normal human kidneys. In situ hybrid ization failed to detect the presence of FGF-1 mRNA in control tissue. In contrast, each stage of the developing glomerular lesion associate d with chronic rejection demonstrated the exaggerated appearance of FG F-1 protein in visceral and parietal epithelial cells. Intense stainin g for FGF-1 protein did not correlate with the increased appearance of FGF-1 mRNA, which was restricted to circulating inflammatory cells. G lomeruli in kidneys with findings of chronic rejection also exhibited increased immunodetection of both FGFR and PCNA in mesangial and epith elial cells. Immunogold labeling of chronically rejected visceral epit helial cells revealed both cytoplasmic and nuclear/localization of FGP -1, thereby establishing mitogenic potential of the growth factor. The enhanced appearance of both biologically active FGF-1 and FGFR sugges ts that this polypeptide may serve as an important mediator of growth responses associated with glomerular lesion development during chronic rejection.