S. Sakamoto et al., INTERCELLULAR-ADHESION MOLECULE-1 AND CD18 ARE INVOLVED IN NEUTROPHILADHESION AND ITS CYTOTOXICITY TO CULTURED SINUSOIDAL ENDOTHELIAL-CELLS IN RATS, Hepatology, 26(3), 1997, pp. 658-663
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.