ROLE OF ADHESION MOLECULES IN THE DEVELOPMENT OF MASSIVE HEPATIC-NECROSIS IN RATS

Massive hepatic necrosis develops after endotoxin administration in ra ts pretreated with heat-killed Propionibacterium acnes as a result of microcirculatory disturbance caused by endothelial cell destruction by activated macrophages in the hepatic sinusoids, Immunohistochemical h epatic expression of intercellular adhesion molecule-1 (ICAM-1) and ly mphocyte function-associated antigen 1 alpha (LFA-1 alpha) and the eff ect of monoclonal antibodies against both adhesion molecules on liver necrosis provoked after endotoxin administration was studied in these rats, There were increased stains of ICAM-1 in endothelial cells and L FA-1 alpha in macrophages in the hepatic sinusoids in Propionibacteriu m acnes-pretreated rats compared with normal rats, Such stains were fu rther increased soon after endotoxin administration, followed by devel opment of hepatic necrosis. Monoclonal antibodies against both adhesio n molecules significantly attenuated the extent of liver injury compar ed with controls, without affecting the infiltration and activation of hepatic macrophages. Polyclonal antibodies against polymorphonuclear leukocytes eradicated circulating neutrophils, but did not change such liver injury, although gum arabic, which suppressed macrophage activa tion, attenuated the extent of Liver injury, Thus, adhesion between en dothelial cells and activated macrophages in the hepatic sinusoids via ICAM-1 and LFA-1 alpha is essential for the initiation of massive hep atic necrosis of this type. Contribution of neutrophils seems less lik ely.