Enhancement of phagocytosis and cytotoxicity in macrophages by tumor-derived IL-18 stimulation
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Inoculation of mice with the murine NFSA cell line caused theformation of large tumors with necrotic tumor cores. FACSanalysis revealed accumulations of CD11b+ cells in the tumors. Microarray analysis indicated that the NFSA cells expressed ahigh level of the pro-inflammatory factor interleukin-18 (il-18),which is known to play a critical role in macrophages. However, little is known about the physiological function ofIL-18-stimulated macrophages. Here, we provide directevidence that IL-18 enhances the phagocytosis of RAW264 cellsand peritoneal macrophages, accompanied by the increasedexpression of tumor necrosis factor (tnf-α), interleukin-6 (il-6)and inducible nitric oxide synthase (Nos2). IL-18-stimulatedRAW264 cells showed an enhanced cytotoxicity to endothelialF-2 cells via direct cell-to-cell interaction and the secretion ofsoluble mediators. Taken together, our results demonstrate thattumor-derived IL-18 plays an important role in the phagocytosisof macrophages and that IL-18-stimulated macrophages maydamage tumor endothelial cells.
Abstract
Inoculation of mice with the murine NFSA cell line caused theformation of large tumors with necrotic tumor cores. FACSanalysis revealed accumulations of CD11b+ cells in the tumors. Microarray analysis indicated that the NFSA cells expressed ahigh level of the pro-inflammatory factor interleukin-18 (il-18),which is known to play a critical role in macrophages. However, little is known about the physiological function ofIL-18-stimulated macrophages. Here, we provide directevidence that IL-18 enhances the phagocytosis of RAW264 cellsand peritoneal macrophages, accompanied by the increasedexpression of tumor necrosis factor (tnf-α), interleukin-6 (il-6)and inducible nitric oxide synthase (Nos2). IL-18-stimulatedRAW264 cells showed an enhanced cytotoxicity to endothelialF-2 cells via direct cell-to-cell interaction and the secretion ofsoluble mediators. Taken together, our results demonstrate thattumor-derived IL-18 plays an important role in the phagocytosisof macrophages and that IL-18-stimulated macrophages maydamage tumor endothelial cells.
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