De novo induction of endothelial L-selectin ligands during kidney allograft rejection.
Acute kidney allograft rejection is characterized by a lymphocyte infiltration. L-selectin on lymphocytes and its endothelial glycosylated ligands are instrumental in the initiation of lymphocyte extravasation to sites of inflammation. From more than 500 core biopsy specimens taken from kidneys after transplantation, 250 biopsies were graded to have signs of acute rejection. Of these, 52 biopsies with various grades of histologic signs of acute rejection were selected for the study. Controls were 15 biopsies taken within 30 min after revascularization and 10 specimens from well-functioning allografts showing no clinical or histologic evidence of rejection. Immunochemical stainings with monoclonal antibodies against functionally active decorated L-selectin ligands. i.e., sialyl-Lewis x (sLex, 2F3 and HECA-452) or sulfated lactosamine (MECA-79) were performed. Although no endothelial 2F3 and MECA-79 epitopes were detected in nonrejecting control specimens, the expression was induced at the onset and during acute allograft rejections. The level of expression (in semi-quantitative score) of 2F3 reactivity correlated with the severity of rejection (P<0.0001, grade I versus grade IIB), and the level of expression decreased as the rejection resolved. Kidney biopsies taken shortly after revascularization and thus undergoing reperfusion injury showed endothelial staining with another anti sLex antibody, HECA-452. This staining disappeared from well-functioning grafts and reappeared at the onset of an acute allograft rejection. These results suggest that expression of functionally active, properly glycosylated L-selectin ligands might have a role in reperfusion injury and in the initiation of acute rejections after human kidney allograft transplantation.
Kirveskari
Juha
J
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland.|Helsinki University Central Hospital Laboratory Diagnostic, Helsinki, Finland.
Paavonen
Timo
T
Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.|Helsinki University Central Hospital Laboratory Diagnostic, Helsinki, Finland.
Häyry
Pekka
P
Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.|Helsinki University Central Hospital Laboratory Diagnostic, Helsinki, Finland.
Renkonen
Risto
R
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland.|Helsinki University Central Hospital Laboratory Diagnostic, Helsinki, Finland.
D000606:Amino Sugars / Q000378:metabolism*; D000911:Antibodies, Monoclonal; D004727:Endothelium / Q000378:metabolism; D006084:Graft Rejection / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D016030:Kidney Transplantation; D019041:L-Selectin / Q000378:metabolism*; D008024:Ligands; D009844:Oligosaccharides / Q000378:metabolism*; D011184:Postoperative Period; D000080506:Sialyl Lewis X Antigen; D013997:Time Factors; D014184:Transplantation, Homologous
D000606:Amino Sugars; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D008024:Ligands; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D019041:L-Selectin; C032233:lactosamine