Sala A, Testa T, Folco G
Center for Cardiopulmonary Pharmacology, Institute of Pharmacological Sciences, University of Milan, Italy.
FEBS Lett. 1996 Jun 17;388(2-3):94-8. doi: 10.1016/0014-5793(96)00539-x.
The production of leukotriene A4 (LTA4)-derived metabolites, analysed by RP-HPLC, was studied in purified bovine polymorphonuclear leukocyte (PMNL) preparations and in PMNL-platelet coincubations after challenge with the calcium ionophore A23187. The results obtained show that in bovine PMNL LTB4 represents the main LTA4 metabolite. When washed platelets were added to PMNL, LTC4 was the main enzymatic metabolite observed, indicating a substantial transfer of PMNL-derived LTA4 to platelets. The synthesis of LTC4 was accompanied by a significant decrease in LTB4, suggesting that a quota of the LTB4 synthesized in PMNL preparations is the result of transcellular metabolism of released LTA4 by neighbouring PMNL. Reduction of PMNL-PMNL interactions through dilution of cell incubates allowed us to estimate that most of the leukotriene A4 synthesized by PMNL is indeed released from the cell. LTA4, and not LTB4, represents the main 5-lipoxygenase metabolite released by bovine PMNL.
采用反相高效液相色谱法(RP-HPLC)分析了白三烯A4(LTA4)衍生代谢产物的生成情况,研究对象为纯化的牛多形核白细胞(PMNL)制剂以及在用钙离子载体A23187刺激后的PMNL与血小板共孵育体系。所得结果表明,在牛PMNL中,白三烯B4(LTB4)是主要的LTA4代谢产物。当将洗涤后的血小板添加至PMNL时,观察到白三烯C4(LTC4)是主要的酶促代谢产物,这表明PMNL衍生的LTA4大量转移至血小板。LTC4的合成伴随着LTB4的显著减少,这表明在PMNL制剂中合成的一部分LTB4是邻近PMNL释放的LTA4经跨细胞代谢的结果。通过稀释细胞培养液减少PMNL与PMNL之间的相互作用,使我们能够估计PMNL合成的大部分白三烯A4确实从细胞中释放出来。LTA4而非LTB4是牛PMNL释放的主要5-脂氧合酶代谢产物。