Inhibition of phytohemagglutinin-induced lymphocyte mitogenesis by lipoxygenase metabolites of arachidonic acid: structure-activity relationships.
Inhibition of phytohemagglutinin-induced lymphocyte mitogenesis by lipoxygenase metabolites of arachidonic acid: structure-activity relationships.
复制标题
花生四烯酸脂氧合酶代谢物抑制植物血凝素诱导的淋巴细胞有丝分裂：结构-活性关系。
作者：
C. Low;M. Pupillo;R. Bryant;J. Bailey
微摩尔浓度的羟基二十碳四烯酸(HETE‘s)可完全抑制植物血凝素(PHA)诱导的小鼠混合淋巴细胞有丝分裂。这些是花生四烯酸的脂氧合酶代谢产物，在适当的刺激下，巨噬细胞、淋巴细胞和免疫系统的其他组件会合成相当浓度的花生四烯酸。在这里描述的研究中，检查了最大反辐射活性的结构要求。以花生四烯酸为底物，采用单线态氧光化学法或酶促合成法制备了一系列单羟化HETE，并用高效液相色谱法进行了分离。以合适的不饱和脂肪酸为底物合成了含有不同双键数目的异构体，并用不同的乙酰氧基和甲氧基的衍生物测试了羟基和羧基的功能重要性。无血清有丝分裂试验系统用于测试，它最大限度地减少了脂肪酸与血清蛋白的结合，并将各种HETE的抑制效力提高了数倍。研究发现，抑制细胞增殖与羟基靠近二十碳四烯酸中心有关，其顺序为：9大于11大于12大于15大于8远大于5；脂肪酸链上的双键数目依次为：15-OH、20：4大于15-OH、20：3远大于15-OH、20：2远大于15-OH、20：0；和15位官能团以及1-羧基，按顺序递减：15-羟基，大于15-乙酰氧基的1-羧基，远大于15-羟基的1-羧基，大于15-乙酰氧基的1-甲氧基，1-甲氧基。
Phytohemagglutinin (PHA)-induced mitogenesis of mixed mouse spleen lymphocyte populations, measured by [3H]thymidine incorporation, was completely inhibited by micromolar concentrations of certain hydroxyeicosatetraenoic acids (HETE's). These are lipoxygenase metabolites of arachidonic acid which are synthesized in considerable concentrations by macrophages, lymphocytes, and other components of the immune system when appropriately stimulated. In the studies described here, the structural requirements for the maximum antimitogenic activities were examined. A series of monohydroxylated HETE's were prepared using a singlet oxygen photochemical procedure or by enzymatic synthesis from arachidonic acid substrate, and isolated by HPLC. Isomers containing different numbers of double bonds were synthesized using the appropriate unsaturated fatty acid as substrate, and the functional importance of the OH and carboxylic functions was tested using various acetoxy- and carbomethoxy derivatives. A serum-free mitogenesis assay system was used for testing, which minimized binding of the fatty acids by serum proteins and increased the inhibitory potency of the various HETE's several-fold. It was found that inhibition of cell proliferation was related to: hydroxyl proximity to the center of the eicosatetraenoic acid, decreasing in the order: 9 greater than 11 greater than 12 greater than 15 greater than 8 much greater than 5; the number of double bonds in the fatty acid chain, decreasing in the order: 15-OH, 20:4 greater than 15-OH 20:3 much greater than 15-OH, 20:2 much greater than 15-OH, 20:0; and the 15-position functional group as well as the 1-carboxylic group, decreasing in the order: 15-hydroxy, 1-carboxylic greater than 15-acetoxy, 1-carboxylic much greater than 15-hydroxy, 1-carbomethoxy greater than 15-acetoxy, 1-carbomethoxy.(ABSTRACT TRUNCATED AT 250 WORDS)
羟基类二十烷酸对白细胞和血小板脂氧合酶的调节。
影响因子：
5.8
作者：
Vanderhoek,JY;Bryant,RW;Bailey,JM
通讯作者：
Bailey,JM