Sialyl Lewisx‐ and L‐selectin‐dependent site‐specific lymphocyte extravasation into renal transplants during acute rejection

Abstract

Kidney allograft rejection is an inflammatory process dominated by lymphocytes. During rejection lymphocytes preferentially adhere to the peritubular capillary endothelium (PTCE), which acquires morphological features common to high endothelium. These observations indicate that PTCE is the site of lymphocyte entry into the rejecting renal allograft. Of the identified endothelial adhesion molecules, ICAM‐1 was already expressed on the endothelium of normal kidneys, and its expression was strongly enhanced during rejection without site‐specific restriction. VCAM‐1 was not expressed on the endothelium of normal or syngeneic kidneys, but its expression was induced during allograft rejection not only in PTCE, but occasionally also on the endothelium of larger vessels. Sialyl Lewis^x (sLe^x) showed a very restricted pattern of expression; endothelium was sLe^x‐negative both in control and syngeneic kidneys. On the other hand, PTCE reacted strongly with anti‐sLe^x antibody in allografts. When kidney frozen sections were treated with sialidase the binding of lymphocytes decreased by 70%. Low‐dose chymotrypsin treatment of lymphocytes, known to remove L‐selectin from the lymphocyte surface, decreased their binding to PTCE by 60%. Likewise lymphocyte adhesion to PTCE was inhibited by 70% by anti‐sLe^x‐ and anti‐L‐selectin‐antibodies and by sLe^x tetrasaccharide. Finally PTCE in the allografts, but not in syngeneic grafts or normal kidneys, bound an L‐selectin‐IgG fusion protein, indicating that ligands for L‐selectin were induced during rejection.