INTERCELLULAR-ADHESION MOLECULE-1 AND CD18 ARE INVOLVED IN NEUTROPHILADHESION AND ITS CYTOTOXICITY TO CULTURED SINUSOIDAL ENDOTHELIAL-CELLS IN RATS

The expression of several adhesion molecules is increased on the hepat ic sinusoidal endothelial cells (SECs) in various liver diseases, The objective of this study is to assess the roles of intercellular adhesi on molecule 1 (ICAM-1) and of CD18 in the interaction between the neut rophils (polymorphonuclear leukocytes [PMNs]) and SECs and in the inju ry to SECs mediated by PMNs, Rat PMNs was perfused on SECs stimulated with tumor necrosis factor alpha (TNF-alpha) using an in vitro flow sy stem. The number of adhered PMNs to SECs and that of PMNs migrated und er SECs was counted and the effects of anti-ICAM-1, anti-CD18, and dex amethasone were studied, We also define the effect of these antibodies on the SEC injury mediated by PMNs stimulated with phorbol 12-myrista te 13-acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP). TNF-alpha significantly increased the adhesion of PMNs to SECs (322 /- 26 cells/mm(2)) compared with controls (194 +/- 22 cells/mm(2)), An ti-ICAM-1 and anti-CD18 significantly inhibited the adhesion of PMNs ( 131 +/- 10 and 51 +/- 30 cells/mm(2), respectively), These antibodies also decreased the migration rate of PMNs (6.0% and 7.9%, respectively ) compared with controls (migration rate, 21.2%), The SEC injury induc ed by PMA- and fMLP-activated PMNs was prevented by anti-ICAM-1 and an ti-CD18, The adhesion of PMNs induced by TNF-alpha was inhibited by th e treatment with dexamethasone (160 +/- 20 cells/mm(2)) via a down-reg ulation of ICAM-1 expression on SECs. The interactions between ICAM-1 and CD18 appeared to be important in the adhesion and the migration of PMNs to SECs. The injury to SECs vias induced by the close interactio n between the activated PMNs and SECs mediated via ICAM-1 and CD18.