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.