L-selectin and its ligands mediate infiltration of mononuclear cells into kidney interstitium after ureteric obstruction.
It was previously reported that the L-selectin ligands detected by a rat L-selectin and human IgG chimeric molecule (rLEC-IgG) are expressed in the distal tubules of the kidney, where no leukocyte traffic is seen under physiological conditions. In the present study, the role of L-selectin ligands in leukocyte infiltration into the kidney interstitium was investigated using a rat ureteric obstruction model. After ligation of the ureter, ligands for L-selectin rapidly disappeared from tubular epithelial cells and were relocated to the interstitium and peritubular capillary walls, where infiltration of monocytes and CD8(+) T cells subsequently occurred. Mononuclear cell infiltration was significantly inhibited by intravenous injection of a neutralizing monoclonal antibody (MAb) against L-selectin, indicating the possible involvement of an L-selectin-mediated pathway. Interestingly, immunohistochemical studies with a MAb against sulphatide showed that the distribution of sulphatide, known to be one of the candidates of L-selectin ligand, was almost indistinguishable from the staining pattern of rLEC-IgG in both normal and ureteric obstructed kidneys, suggesting that sulphatide and/or related molecule(s) relocated to the renal interstitium were recognized by leukocyte L-selectin, leading to interstitial leukocyte infiltration. In line with this notion, intravenous injection of sulphatide markedly inhibited leukocyte infiltration, suggesting that L-selectin-sulphatide interaction may play a pivotal role in interstitial leukocyte infiltration in the kidney following ureteric obstruction.
Department of Medicine III, Okayama University Medical School, Okayama 700-8558, Japan.
K
K
Shikata
Y
Y
Suzuki
J
J
Wada
K
K
Hirata
M
M
Matsuda
H
H
Kawashima
T
T
Suzuki
M
M
Iizuka
H
H
Makino
M
M
Miyasaka
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002855:Chromatography, Thin Layer; D005260:Female; D006801:Humans; D007074:Immunoglobulin G; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000378:metabolism; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D051379:Mice; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013433:Sulfoglycosphingolipids / Q000378:metabolism* / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D013433:Sulfoglycosphingolipids; D019041:L-Selectin