Honda A, Morita I, Murota S, Mori Y
Biochim Biophys Acta. 1986 Jul 18;877(3):423-32. doi: 10.1016/0005-2760(86)90208-0.
The appearance of the arachidonic acid metabolic pathway in human promyelocytic leukemia (HL-60) cells was investigated during 1 alpha,25-dihydroxyvitamin D-3-induced monocytic differentiation. 1 alpha,25-Dihydroxyvitamin D-3-treated HL-60 cells acquired the ability to convert [1-14C]arachidonic acid to thromboxane B2 and prostaglandin E2 during monocytic differentiation. The major cyclooxygenase product synthesized by the HL-60 cells after 3-4 days exposure to 1 alpha,25- dihydroxyvitamin D-3 (48 nM) was thromboxane B2 and its production was about 19-25-times higher than that of untreated HL-60 cells. The percent conversion of thromboxane B2 from [1-14C]arachidonic acid in the 1 alpha,25-dihydroxyvitamin D-3 (48 nM, 3 day exposure)-treated HL-60 cells was about 4.4% as compared to that (about 0.3%) of the untreated cells, whereas the percent conversion of thromboxane B2 from [1-14C]prostaglandin H2 in the 1 alpha,25-dihydroxyvitamin D-3-treated cell homogenate was about 22.4% as compared to that (about 13.6%) of the untreated cell homogenate. The stimulatory effect of 1 alpha,25-dihydroxyvitamin D-3 on thromboxane B2 production from [1-14C]arachidonic acid and from [1-14C]prostaglandin H2 in HL-60 cells was inhibited by the addition of cycloheximide (1 microgram/ml). However, 1 alpha,25-dihydroxyvitamin D-3 (48 nM) did not significantly stimulate the arachidonic acid release either in HL-60 cells or in 1 alpha,25-dihydroxyvitamin D-3-induced cells. These results suggest that the stimulatory effect of 1 alpha,25-dihydroxyvitamin D-3 on the thromboxane production in HL-60 cells was not due to the activation of phospholipase A2 but due to the induction of fatty acid cyclooxygenase and thromboxane synthetase activities. Thromboxane A2 actively produced during the monocytic differentiation of HL-60 cells could influence the cell adhesiveness of the monocyte-macrophage-differentiated cells.
在1α,25 - 二羟基维生素D - 3诱导的人早幼粒细胞白血病（HL - 60）细胞单核细胞分化过程中，对花生四烯酸代谢途径的出现情况进行了研究。经1α,25 - 二羟基维生素D - 3处理的HL - 60细胞在单核细胞分化过程中获得了将[1 - 14C]花生四烯酸转化为血栓素B2和前列腺素E2的能力。在暴露于1α,25 - 二羟基维生素D - 3（48 nM）3 - 4天后，HL - 60细胞合成的主要环氧化酶产物是血栓素B2，其产量比未处理的HL - 60细胞高约19 - 25倍。与未处理细胞（约0.3%）相比，在经1α,25 - 二羟基维生素D - 3（48 nM，暴露3天）处理的HL - 60细胞中，[1 - 14C]花生四烯酸转化为血栓素B2的转化率约为4.4%，而在经1α,25 - 二羟基维生素D - 3处理的细胞匀浆中，[1 - 14C]前列腺素H2转化为血栓素B2的转化率与未处理细胞匀浆（约13.6%）相比约为22.4%。添加放线菌酮（1微克/毫升）可抑制1α,25 - 二羟基维生素D - 3对HL - 60细胞中[1 - 14C]花生四烯酸和[1 - 14C]前列腺素H2生成血栓素B2的刺激作用。然而，1α,25 - 二羟基维生素D - 3（48 nM）对HL - 60细胞或1α,25 - 二羟基维生素D - 3诱导的细胞中的花生四烯酸释放均无显著刺激作用。这些结果表明，1α,25 - 二羟基维生素D - 3对HL - 60细胞中血栓素生成的刺激作用不是由于磷脂酶A2的激活，而是由于脂肪酸环氧化酶和血栓素合成酶活性的诱导。在HL - 60细胞单核细胞分化过程中活跃产生的血栓素A2可能会影响单核细胞 - 巨噬细胞分化细胞的细胞黏附性。
