IMMUNOLOCALIZATION OF ACIDIC FIBROBLAST GROWTH-FACTOR AND RECEPTORS IN THE TUBULOINTERSTITIAL COMPARTMENT OF CHRONICALLY REJECTED HUMAN RENAL-ALLOGRAFTS

Tubular damage and loss associated with interstitial inflammation and fibrosis may be the most important determinants in chronic renal allog raft rejection. To elucidate potential pathophysiologic mechanisms ass ociated with tubulointerstitial lesions, we examined the expression of a fibrogenic cytokine, acidic fibroblast growth factor (FGF-1) and it s high-affinity receptors, in both relevant renal transplant controls (n=5) and tissue from patients (n=19) who underwent nephrectomy after graft loss, secondary to chronic rejection. Pn situ hybridization and immunohistochemical analyses demonstrated minimal expression of FGF-1 mRNA and protein in the tubulointerstitial compartment of the normal h uman kidney. In contrast, tubulointerstitial lesions in kidney allogra fts experiencing chronic rejection demonstrated the exaggerated appear ance of both FGF-1 protein and mRNA in resident inflammatory and tubul ar epithelial cells. Patterns of staining were consistent throughout t ubular compartments and did not appear to be localized to any particul ar region. The tubulointerstitium in kidneys with findings of chronic rejection also exhibited increased immunodetection of proliferating ce ll nuclear antigen in the tubular epithelium, inflammatory cell infilt rate, and neovascular structures. The enhanced appearance of FGF-1 and readily detectable fibroblast growth factor receptors suggests that t his polypeptide mitogen may serve as an important mediator of growth a nd repair responses, associated with development of angiogenesis and t ubulointerstitial lesions during chronic rejection of human renal allo grafts.