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Toxicologic Pathology
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Journal Article

The Phenotypic and Functional Changes of Rat Kupffer Cells Cultured with Interleukin-2

Satoshi Inoue

Kanzakigawa Laboratory, Shionogi Research Laboratories, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka 561, Japan

Akira Yamashita

The 2nd Department of Anatomy, Hamamatsu University School of Medicine, 3600, Handa-cho, Hamamatsu 431-31, Japan

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-µm latex particles was increased by incubating with hrIL-2 (104 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 (104 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.

Key Words: Macrophage antigen • class 2 antigen • Fc receptor • complement receptor • phagocytosis • accessory cell function

Toxicologic Pathology, Vol. 21, No. 1, 71-80 (1993)
DOI: 10.1177/019262339302100109
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