IN-SITU EXPRESSION OF PLATELET-DERIVED GROWTH-FACTOR (PDGF-BETA) DURING CHRONIC REJECTION IS ABOLISHED BY RETRANSPLANTATION

We have shown that Fischer 344 --> Lewis renal allografts (ALLO) devel op chronic rejection which is not detected in Lewis --> Lewis isograft s (ISO). The progression of chronic rejection in ALLO can be reversed by retransplantation (RE-TX) of kidneys from ALLO back into syngeneic Fischer 344 recipients, The purpose of this study was to assess the in situ expression of PDGF-beta, a cytokine associated with wound injury , in ISO, ALLO, and RE-TX. In situ PDGF-beta mRNA expression in kidney sections was assessed early (8 weeks) and late (16 weeks) during the development of chronic rejection. Kidneys from ALLO were transplanted back into syngeneic Fischer recipients at 12 weeks and evaluated for P DGF-beta expression 12 weeks later. Differences in glomerular staining were graded quantitatively on a minimum of 25 glomeruli per section w ith grade 0, no positive cells in the glomerulus; grade 1, 1 or 2 posi tive cells; grade 2, 3 or more positive cells in a segmental distribut ion; and grade 3, >4 positive cells of moderate intensity in a diffuse distribution, According to this grading system, glomerular PDGF-beta mRNA expression in isografts (N = 6) at 8 and 16 weeks after transplan tation was 0.09 +/- 0.03 and 0.2 +/- 0.04, respectively. In allografts (N = 6), PDGF-beta mRNA was significantly higher (P < .001) for the s ame time periods, 1.28 +/- 0.6 and 1.89 +/- 0.08, respectively. in sit u expression of PDGF in retransplants (N = 6) at 24 weeks; 0.07 +/- 0. 02, was significantly diminished (P < .001) at 24 weeks compared to al lografts at 8 or 16 weeks. lit situ expression of PDGF-beta in ALLO co incided with progression of functional changes, including urinary albu min excretion and glomerular macrophage infiltration, during chronic r ejection. Downregulation of PDGF-beta in RE-TX occurred once the progr ession of chronic rejection was reversed. We believe that PDGF-beta ma y mediate chronic rejection in rats. (C) 1995 Academic Press, Inc.