Characterization of high endothelial-like properties of peritubular capillary endothelium during acute renal allograft rejection.

Acute allograft rejection is characterized by leukocyte infiltration. Previously we suggested that the site of entry of lymphocytes into rejecting kidney allografts is the peritubular but not other capillary endothelium. Here we confirm this observation in a frozen section ex vivo binding assay and further characterize the peritubular capillary endothelium during acute kidney allograft rejection. The increase in lymphocyte binding to peritubular capillaries precede the peak of inflammation (leukocyte accumulation) in the graft. Pretreatment of lymphocytes with antibodies against CD 11a and CD 18 (LFA-1 alpha and beta chain, respectively) could decrease the lymphocyte binding, whereas ICAM-1 pretreatment of tissue sections was ineffective. Light- and electromicroscopy revealed a marked activation of peritubular capillary endothelial cells in allografts, whereas these alterations were less severe or absent in syngeneic controls and normal kidneys. Finally our data suggest that the ligand responsible for the binding of lymphocytes to kidney peritubular areas is organ specific. Only mannose-1 phosphate, but not mannose-6 phosphate, could decrease the lymphocyte binding. Y-1, an antibody staining rat lymph node high endothelial venules (HEV), did not react with allograft peritubular capillaries having functional and morphologic similarities to HEV.