title: Mechanism of accumulation of macrophages in galactosamine-induced liver injury: effect of lipoxygenase inhibitors on chemotaxis of spleen cells.
abstract: In an attempt to clarify a mechanism of macrophage infiltration in galactosamine-induced hepatic injury, we investigated chemotactic factor(s) generated by murine hepatocytes exposed to galactosamine. Hepatocytes, isolated from murine liver by perfusion and digestion with collagenase, were incubated with galactosamine. Conditioned medium was collected 24 h later and chemotaxis of murine spleen cells was measured by stimulation of the conditioned medium using a modified Boyden chamber. Chemotactic activity was demonstrated in the conditioned medium of hepatocytes exposed to more than 3 mM galactosamine. Chemotactic activity of the conditioned medium was not reduced after freeze-thawing, and found to be dialyzable (molecular weight < 12,000). Trypsin (0.25%, 37 degrees C, 30 min) or heat (56 degrees C, 30 min) treatment reduced chemotactic activity of the conditioned medium. Furthermore, chemotaxis of spleen cells was decreased in the presence of lipoxygenase inhibitors (azelastine, ketotifen). These results suggest that accumulation of macrophages in the liver could be mediated by chemotactic factor produced by the galactosamine-treated hepatocytes, and that this mechanism may contribute to the pathogenesis of hepatic injury induced by galactosamine.
authors.affiliation: Department of Gastroenterology and Hepatology, Koshigaya Hospital, Dokkyo University School of Medicine, Saitama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shiratori
authors.forename: K
authors.initials: K
authors.lastname: Hai
authors.forename: H
authors.initials: H
authors.lastname: Takada
authors.forename: H
authors.initials: H
authors.lastname: Kiriyama
authors.forename: T
authors.initials: T
authors.lastname: Nagura
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Kamii
authors.forename: K
authors.initials: K
authors.lastname: Okano
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000032:analysis / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects* / Q000502:physiology; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D005688:Galactosamine / Q000494:pharmacology*; D007665:Ketotifen / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D008297:Male; D051379:Mice; D010793:Phthalazines / Q000494:pharmacology; D013154:Spleen / Q000166:cytology* / Q000378:metabolism / Q000502:physiology
chemical_list: D016227:Benzoquinones; D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D016859:Lipoxygenase Inhibitors; D010793:Phthalazines; D005688:Galactosamine; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D007665:Ketotifen; C020976:azelastine