Henderson W R, Rashed M, Yong E C, Fritsche T R, Chiang G K
Department of Medicine, University of Washington, Seattle 98195.
Biochemistry. 1992 Jun 16;31(23):5356-62. doi: 10.1021/bi00138a016.
We have recently demonstrated a novel cytotoxic effect of human platelets against Toxoplasma gondii and a role for thromboxane (TX) in this process (Yong et al., 1991). We now report on the spectrum of lipid mediators released by human platelets after interaction with T. gondii. In addition to TXB2, human platelets after incubation with T. gondii for 90 min released 12-hydroxyheptadecatrienoic acid (12-HHT), 12-hydroxyeicosatetraenoic acid (12-HETE), and an unidentified peak (UVmax 234 nm) as determined by reverse-phase high-performance liquid chromatography. Thermospray-liquid chromatography/mass spectrometry analysis and straight-phase HPLC identified the unknown peak as a mixture of 13-hydroxyoctadecadienoic acid (HODE) and 9-HODE. Radiolabeling studies with [14C]linoleic acid indicated that the platelets were the cellular source of the octadecanoids with 13-HODE (87.7%) greater than 9-HODE (12.3%). Inhibitor studies with indomethacin indicated that 13-HODE was a lipoxygenase product and 9-HODE was a cyclooxygenase product of linoleic acid. Thus, Toxoplasma-stimulated platelets release oxygenated products of both arachidonic acid and linoleic acid which may be important in the host response to T. gondii infection.
我们最近证实了人血小板对刚地弓形虫具有一种新的细胞毒性作用,并且血栓素(TX)在此过程中发挥了作用(Yong等人,1991年)。我们现在报告人血小板与刚地弓形虫相互作用后释放的脂质介质谱。除了TXB2外,人血小板与刚地弓形虫孵育90分钟后,通过反相高效液相色谱法测定还释放了12-羟基十七碳三烯酸(12-HHT)、12-羟基二十碳四烯酸(12-HETE)以及一个未鉴定的峰(紫外最大吸收波长234nm)。热喷雾液相色谱/质谱分析和正相高效液相色谱鉴定该未知峰为13-羟基十八碳二烯酸(HODE)和9-HODE的混合物。用[14C]亚油酸进行的放射性标记研究表明,血小板是这些十八碳类化合物的细胞来源,其中13-HODE(87.7%)比9-HODE(12.3%)含量更高。用吲哚美辛进行的抑制剂研究表明,13-HODE是亚油酸的脂氧合酶产物,9-HODE是亚油酸的环氧化酶产物。因此,刚地弓形虫刺激的血小板释放花生四烯酸和亚油酸的氧化产物,这可能在宿主对刚地弓形虫感染的反应中起重要作用。