砂ネズミ脳血管内皮細胞に及ぼす各種サイトカインの影響

EFFECTS OF CYTOKINES ON CULTURED MICROVASCULAR ENDOTHELIAL CELLS DERIVED FROM GERBIL BRAIN

　抄録　砂ネズミの脳微小血管内皮細胞を分離培養し，ここに，tumor necrosis factor （TNF），interferon-γ（γIFN）を投与してその影響を検討したところ，TNF 1000U／ml以上の投与により，内皮細胞のDNA合成能は70％近くも抑制され，形態学的にも，細胞の紡錘化，オーバーラップが観察された。γIFN投与では何の変化も起こらなかった。一方，短期培養ヒトglioma細胞の培養上清を用いて，同様の検討を行ったところ，12例中6例に，50％以上に及ぶDNA合成能の抑制をみた。又，この強い抑制を受けた6例とも，抗TNF抗体の添加により，抑制は解除され，培養上清中に，TNF類似活性の存在が示唆された。

We studied the effects of cytokines on cultured microvascular endothelial cells derived from gerbil brain. Microvascular endothelial cells were de-rived from the endothelial cells of gerbil brain. First, effects of tumor necrosis factor (TNF) or [³H] thymidin up-take by the endothelial cells and human smooth muscle cells were studied. After 4 days exposure to TNF, 50 μCi/ml of [³H] thymi-dine were added to these cells. [³H] thymidine up-take by the endothelial cells were suppressed by adding TNF dose-dependently. Especially, [³H] thymidine up-take by endothelial cells cultured with 1000 U/ml TNF for 4 days were 25 to 62% of the control values. These cells exposed to 1000 U/ml TNF, furtheremore, became spindlelike in appearance and over up each other. But, TNF had no effects on human smooth muscle cells.

Second, instead of TNF, interferone-γ(γIFN) were studied in the same way. But, [³H] thymi-dine up-take by the endothelial cells were not ef-fected by adding γfFN.

Third, the supernatant of the cultured glioma cells were studied in the same way. The super-natants of 6 glioma cells in 8 cases showed TNF like activity to the endothelial cells of gerbil brain. These supernatants, that is, suppressed [³H] thymi-dine up-take by the endothelial cells over 50%. These suppression were, furthermore, released by adding 50 μd anti-TNF antibodies. So, we found the cytotoxic effects of TNF on the endothelial cells of gerbil brain. The supernatants of glioma cells, also, showed TNF like activity to the endothelial cells.