Increased glomerular deposits of Von Willebrand factor in chronic, but notacute, rejection of primate renal allografts

Background. In our previously described primate renal allograft model, T ce ll ablation leads to longterm graft survival. The role of endothelial cell alteration in chronic rejection was examined in our model. Methods. Renal transplants were performed in rhesus monkeys using a T cell- depleting immunotoxin, FN18-CRM9. Sections from 10 rejected kidneys (5 acu te and 7 chronic rejection) were examined after immunohistochemical stainin g for expression of endothelium-related proteins [von Willebrand factor (vW F), CD62P, and CD31], fibrinogen, and a macrophage marker (CD68), Glomerula r staining for each antigen was graded on a semiquantitative scale. Results. Intense staining for vWF was consistently observed in glomerular e ndothelium, subendothelium, and mesangium in all kidneys removed due to chr onic rejection, vWF staining was weak in kidneys showing acute rejection. T he difference in glomerular staining was statistically significant. Stainin g for vWF in extraglomerular vessels was nearly identical in kidneys showin g acute and chronic rejection. Expression of CD62P was increased in extragl omerular vessels in allografts with chronic rejection, but the glomeruli sh owed little or no staining. There was no significant difference in the glom erular staining for CD62P or CD31 in organs showing acute and chronic rejec tion, Fibrinogen staining of glomerular mesangium was seen in kidneys with chronic rejection. Macrophages (CD68+) infiltrating glomeruli were more num erous in kidneys showing chronic rejection. Conclusion. Increased glomerular deposition of vWF in renal allografts show ing chronic rejection, without increased staining for CD62P or CD31, sugges ts increased constitutive secretion of vWF from endothelial cells as a comp onent of the mechanism of chronic rejection in our model.