INVOLVEMENT OF ACTIVATED POLYMORPHONUCLEAR LEUKOCYTES IN GALACTOSAMINE-INDUCED HEPATIC-INJURY IN RATS

This study attempted to elucidate the pathological role of peripheral blood polymorphonuclear leukocytes (PMNs) in the damage to hepatic sin usoidal endothelial cells (HSECs) in hepatic injury. Wistar male rats weighing about 200 g received a single injection of 1 g/kg body weight of galactosamine (GalN) intraperitoneally for the induction of hepati tis. The level of serum glutamic pyruvate transaminase activity increa sed time-dependently concomitantly with serum endotoxin level and hepa tic lipid peroxide content. Histological studies using light and elect ron microscopy showed that a large number of PMNs infiltrated the midz onal area of the liver and that HSECs in contact with the PMNs were in jured 6 h after GalN injection. Superoxide anion production by PMNs is olated from the peripheral blood of rats treated with GalN was increas ed significantly compared with that from control rats, as estimated by the reduction of exogenously added cytochrome c in the presence of ph orbol myristate acetate. A cytotoxicity study using the Cr-51 release assay revealed that PMNs isolated from GalN-treated rats caused more s erious injury to the HSECs than those from control rats. These results suggest that the oxygen-derived free radicals released from the activ ated PMNs directly injure HSECs and lead to a disturbance of sinusoida l microcirculation. causing an extended liver cell necrosis in GAlN he patitis.