De novo induction of endothelial L-selectin ligands during kidney allograft rejection

Acute kidney allograft rejection is characterized by a lymphocyte infiltrat ion. L-selectin on lymphocytes and its endothelial glycosylated ligands are instrumental in the initiation of lymphocyte extravasation to sites of inf lammation. From more than 500 core biopsy specimens taken from kidneys afte r transplantation, 250 biopsies were graded to have signs of acute rejectio n. Of these, 52 biopsies with various grades of histologic signs of acute r ejection were selected for the study. Controls were 15 biopsies taken withi n 30 min after revascularization and 10 specimens from well-functioning all ografts showing no clinical or histologic evidence of rejection. Immunochem ical stainings with monoclonal antibodies against functionally active decor ated L-selectin ligands. i.e., sialyl-Lewis x (sLex, 2F3 and HECA-452) or s ulfated lactosamine (MECA-79) were performed. Although no endothelial 2F3 a nd MECA-79 epitopes were detected in nonrejecting control specimens, the ex pression was induced at the onset and during acute allograft rejections. Th e level of expression tin semiquantitative score) of 2F3 reactivity correla ted with the severity of rejection (P < 0.0001, grade I versus grade IIB), and the level of expression decreased as the rejection resolved. Kidney bio psies taken shortly after revascularization and thus undergoing reperfusion injury showed endothelial staining with another anti sLex antibody, HECA-4 52. This staining disappeared from well-functioning grafts and reappeared a t the onset of an acute allograft rejection. These results suggest that exp ression of functionally active, properly glycosylated L-selectin ligands mi ght have a role in reperfusion injury and in the initiation of acute reject ions after human kidney allograft transplantation.