The phenotypic and functional changes of rat Kupffer cells cultured with interleukin-2.
We examined the direct effects of human recombinant interleukin 2 (hrIL-2) in vitro on the phenotypic and the functional changes of rat Kupffer cells (KCs) isolated by collagenase perfusion and differential centrifugation. When KCs were cultured with high concentrations of hrIL-2, marked changes were dose-dependently observed in phenotypic expression, phagocytic activity, and accessory cell function compared to untreated KCs. In the phenotypic changes, approximately 70% of KCs expressed class 2 antigen after 48-hr culture. Moreover, rapid expression of iC3b receptor on KCs was observed after 6 hr culture. KC phagocytic activity of both 0.81- and 2-microns latex particles was increased by incubating with hrIL-2 (10(4) U/ml) as compared to those of untreated KCs. Complement-mediated phagocytosis was more dominant than that of Fc receptor-mediated phagocytosis without hrIL-2 and augmented by increasing concentrations of hrIL-2. Accessory cell function of KCs was greatly augmented by preincubation with hrIL-2 (10(4) U/ml) for 24 hr. In the presence of 10(-6) M of indomethacin or prostaglandin E2, accessory cell function was at a lower level than without. This suppressive effect of indomethacin or prostaglandin E2 was reduced at lower concentrations. These results suggest that the potential ability of hrIL-2-activated KCs is closely associated with the ongoing pathophysiological process in the liver during IL-2 immunotherapy.
Kanzakigawa Laboratory, Shionogi & Co., Ltd., Toyonaka, Japan.
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Inoue
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Yamashita
D000818:Animals; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D007376:Interleukin-2 / Q000633:toxicity*; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007840:Latex; D008107:Liver Diseases / Q000473:pathology; D008297:Male; D010587:Phagocytosis / Q000187:drug effects; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains; D017463:Receptors, Complement 3b / Q000502:physiology
D007376:Interleukin-2; D007840:Latex; D017463:Receptors, Complement 3b