Zakrzewski J T, Sampson A P, Evans J M, Barnes N C, Piper P J, Costello J F
Department of Thoracic Medicine, King's College School of Medicine and Dentistry, London.
Prostaglandins. 1988 Jun;35(6):869-83. doi: 10.1016/0090-6980(88)90113-x.
The metabolism of exogenous leukotriene B4 (LTB4) was investigated in venous blood obtained from normal and asthmatic subjects. Using specific radioimmunoassay (RIA) and reverse-phase high performance liquid chromatography (RP-HPLC) techniques we have demonstrated that LTB4 is relatively stable during a 2 hr incubation period at 37 degrees C in our system in vitro. Nevertheless, chromatographic analysis revealed the presence of two products which had retention times identical to 20-hydroxy LTB4 (20-0H LTB4) and 20-carboxy LTB4 (20-C00H LTB4) in which the dicarboxylic derivative was the main metabolite present after 15 min incubation. The amount of LTB4 and its w-oxidation products observed after a 2 hr incubation period was 73% and 24% respectively. There was no basal release of LTB4 from blood. The appearance of these oxidative products was totally suppressed at 4 degrees C and with incubations performed with either venous plasma or Hartmann's control. No significant difference was observed in substrate metabolism between normal and asthmatic subjects. Our results demonstrate that LTB4 is slowly degraded in human whole blood through a cellular dependent process of w-oxidation which may be an important pathway for regulating the availability of this potent biologically active substance.
我们对从正常人和哮喘患者采集的静脉血中外源性白三烯B4（LTB4）的代谢情况进行了研究。通过使用特异性放射免疫测定法（RIA）和反相高效液相色谱法（RP - HPLC）技术，我们证明在我们的体外系统中，LTB4在37℃下2小时的孵育期内相对稳定。然而，色谱分析显示存在两种产物，其保留时间与20 - 羟基LTB4（20 - OH LTB4）和20 - 羧基LTB4（20 - COOH LTB4）相同，其中二羧酸衍生物是孵育15分钟后存在的主要代谢产物。孵育2小时后观察到的LTB4及其ω - 氧化产物的量分别为73%和24%。血液中不存在LTB4的基础释放。这些氧化产物的出现在4℃以及用静脉血浆或哈特曼氏对照进行孵育时被完全抑制。正常人和哮喘患者之间在底物代谢方面未观察到显著差异。我们的结果表明，LTB4在人全血中通过细胞依赖性的ω - 氧化过程缓慢降解，这可能是调节这种强效生物活性物质可用性的重要途径。
