Cytokine secretion and phagocytosis are attenuated in the macrophages in Vegfr-1 tk^–/– mice. (A-B) Mouse peritoneal macrophages were stimulated with hVEGF-A (100 ng/mL), and then levels of cytokines (IL-6 and VEGF-A) secreted into the medium were measured by ELISA after a 48-hour incubation. (A) IL-6 was secreted in response to hVEGF-A, and this secretion was partially suppressed by VEGFR inhibitors, SU5416 and KRN633. Secretion of IL-6 from Vegfr-1 tk^–/– macrophages was low compared with that from the wild-type macrophages. (B) Mouse VEGF-A (mVEGF-A) was secreted from macrophages in the absence of hVEGF-A, and the secretion increased on stimulation with exogenous hVEGF-A. The secretion of mVEGF-A was partially suppressed by VEGFR inhibitors. The secretion from Vegfr-1 tk^–/– macrophages was about half that from wild-type macrophages. Results represent the mean ± SEM from 2 to 3 experiments. (C) The mRNA expression of Il-6 and Vegf-A on treatment with hVEGF-A was examined by real-time RT-PCR analysis. Il-6 is weakly expressed in Vegfr-1 tk^–/– macrophages. Vegf-A expression in Vegfr-1 tk^–/– macrophages is about half that in the wild-type. (D) Macrophages derived from wild-type BM cells in cultures phagocytized dextran and LPS (upper row). On the other hand, macrophages from Vegfr-1 tk^–/– BM did not show strong phagocytosis (lower row). Results are representative of at least 3 independent experiments. The data represent the mean ± SEM. *P < .05, **P < .01; wild-type versus Vegfr-1 tk^–/– macrophages.