THE ROLE OF SELECTINS AND CD18 IN LEUKOTRIENE B-4-MEDIATED WHITE BLOOD-CELL EMIGRATION IN HUMAN SKIN-GRAFTS TRANSPLANTED ON SCID MICE

The purpose of this study was to examine the role of selectins and CD1 8 cell adhesion molecules (CAMs) in inflammation induced by injection of leukotriene B-4 (LTB(4)) into human skin. To accomplish this, the e xpression of CAMs and the ability of specific antibodies against CAMs to block white blood cell (WBC) transmigration were studied in an in v ivo model consisting of human skin transplanted onto mice with the sev ere combined immune deficiency (SCID) mutation. The results indicate t hat LTB(4)-induced WBC transmigration in the human/SCID model is rapid and pronounced; however, it is not accompanied by a significant upreg ulation of the baseline expression of endothelial P-selectin, E-select in, ICAM-1 or VCAM-1. An anti-murine CD18 mAb markedly inhibited white cell infiltration (89% inhibition) confirming the importance of beta( 2) integrins in the process. The role of selectins was also examined. MEL-14 a bioactive antibody against murine L-selectin inhibited transm igration by 66%. A significant, but smaller, effect (39% inhibition) w as observed by blocking E-selectin function. These results indicate th at LTB(4)-induced inflammation does not require upregulation of endoth elial CAM expression and, in contrast to TNF alpha-induced transmigrat ion, is only partially blocked by anti-E-selectin antibodies.