CHEMOTACTIC FACTORS RELEASED FROM HEPATOCYTES EXPOSED TO ACETAMINOPHEN

To clarify the mechanism of neutrophil infiltration in the liver of ac etaminophen-induced hepatic injury, chemotactic factor released from h epatocytes exposed to acetaminophen has been investigated. Hepatocytes exposed to acetaminophen release nondialyzable chemotactic factor, al though acetaminophen in itself inhibits chemotaxis of neutrophils. Che motactic activity of the nondialyzable chemotactic factor was reduced after treatment with heat (56 degrees C, 30 min) or trypsin. Chemotact ic activity was demonstrated at the molecular weights of around 25 and 55 kDa. Chemotactic activity of the conditioned medium was not signif icantly reduced in the presence of antibody against rat KC/gro protein (interleukin-8-related cytokine in rodent). Chemotactic activity of a 25-kDa factor was reduced by the antibody against KC/gro protein, but that of a 55-kDa factor was not reduced. Immunoblot analysis revealed that the peptide reacted with antibody against rat KC/gro protein was demonstrated at a molecular weight of around 20-25 kDa, but not at ar ound 55kDa, when the conditioned medium of acetaminophen-treated hepat ocytes was electrophoresed. These results suggest that hepatocytes exp osed to acetaminophen release two types of chemotactic factors for neu trophils and that a major part of the chemotactic factor could be diff erent from a member of interleukin-8 family.