Rejection of peritubular capillaries in renal allo- and xeno-graft.

Abstract

The microvasculature plays an important role in the pathogenesis of humoral- and cell-mediated renal allo- and xeno-graft rejection. Peritubular capillary (PTC) endothelium expresses the major histocompatibility complex (MHC) class I and II antigens in the resting phase, as does the glomerular capillary endothelium, suggesting that these cells may be major immune targets. However, the role of PTCs in renal allo- and xeno-graft rejection is unclear. In this review, we discuss injury and subsequent remodeling of PTCs in both humoral- and cell-mediated rejection in allo- and xeno-grafts. Recent evidence suggests that PTC injury and endothelial cell death occur during both cell- and humoral-mediated rejection. Severe PTC rejection contributes to deterioration of graft function and acute graft loss. The mild but recurrent form of PTC rejection is associated with progressive interstitial fibrosis and chronic rejection. Following endothelial injury, the remaining PTC endothelium activates with up-regulation of allo-antigens and adhesion molecules, and down-regulation of anti-coagulant proteins. Subsequent to this, more severe rejection and graft dysfunction occur. Therefore, a careful analysis of cellular- and antibody-mediated rejection in PTCs is important in the diagnosis of rejection, prediction of graft prognosis, and in further development of new anti-rejection therapies.