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 sinusoidal endothelial cells (HSECs) in hepatic injury. Wistar male rats weighing about 200g received a single injection of 1g/kg body weight of galactosamine (GalN) intraperitoneally for the induction of hepatitis. The level of serum glutamic pyruvate transaminase activity increased time-dependently concomitantly with serum endotoxin level and hepatic lipid peroxide content. Histological studies using light and electron microscopy showed that a large number of PMNs infiltrated the midzonal area of the liver and that HSECs in contact with the PMNs were injured 6h after GalN injection. Superoxide anion production by PMNs isolated from the peripheral blood of rats treated with GalN was increased significantly compared with that from control rats, as estimated by the reduction of exogenously added cytochrome c in the presence of phorbol myristate acetate. A cytotoxicity study using the 51Cr release assay revealed that PMNs isolated from GalN-treated rats caused more serious injury to the HSECs than those from control rats. These results suggest that the oxygen-derived free radicals released from the activated PMNs directly injure HSECs and lead to a disturbance of sinusoidal microcirculation, causing an extended liver cell necrosis in GalN hepatitis.