Yang M, Wu W, Mirocha C J
Department of Poultry Science, University of Wisconsin, Madison, USA.
Immunopharmacol Immunotoxicol. 1996 Nov;18(4):597-608. doi: 10.3109/08923979609052756.
The direct effects of wortmannin (0 to 1280 nM) on several functions in cultured macrophages isolated from Sephadex-elicited Leghorn chicken peritonea were studied. Under concentrations not affecting cell viability, wortmannin, as low as 5 nM, inhibited lipopolysaccharide (LPS)-induced nitric oxide production (P < 0.01). However, wortmannin (as high as 1280 nM) exposure 5 hours post LPS induction had no effect on nitric oxide production in macrophages, indicating a blockade of LPS-induction of a signaling pathway related to nitric oxide formation. Phorbol myristate acetate (PMA)-induced superoxide production was only inhibited (P < 0.001) by concurrent exposure to 1280 nM wortmannin. Prior exposure to 160 nM and higher of wortmannin for 24 hours reduced the average number of yeast cells ingested by or attached to a single macrophage (P < 0.001) and the ability of the macrophage to kill the baker's yeast (P < 0.05), while wortmannin itself did not affect the yeast. These data provide direct evidence for macrophages being the target cell of wortmannin and further support the notion that impaired macrophage functions are responsible for the immunosuppressive effect of wortmannin previously observed in birds.
研究了渥曼青霉素（0至1280 nM）对从葡聚糖诱导的来亨鸡腹膜分离的培养巨噬细胞中几种功能的直接影响。在不影响细胞活力的浓度下，低至5 nM的渥曼青霉素就能抑制脂多糖（LPS）诱导的一氧化氮生成（P < 0.01）。然而，在LPS诱导后5小时暴露于高达1280 nM的渥曼青霉素对巨噬细胞中的一氧化氮生成没有影响，这表明与一氧化氮形成相关的信号通路的LPS诱导被阻断。佛波酯（PMA）诱导的超氧化物生成仅在同时暴露于1280 nM渥曼青霉素时受到抑制（P < 0.001）。预先暴露于160 nM及更高浓度的渥曼青霉素24小时会减少单个巨噬细胞摄取或附着的酵母细胞的平均数量（P < 0.001）以及巨噬细胞杀死面包酵母的能力（P < 0.05），而渥曼青霉素本身对酵母没有影响。这些数据为巨噬细胞是渥曼青霉素的靶细胞提供了直接证据，并进一步支持了巨噬细胞功能受损是渥曼青霉素先前在鸟类中观察到的免疫抑制作用的原因这一观点。
