Abdel Baset H, O'Neill G P, Ford-Hutchinson A W
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, Quebec, Canada.
Mol Biochem Parasitol. 1995 Jul;73(1-2):31-41. doi: 10.1016/0166-6851(95)00085-f.
Schistosoma mansoni has previously been reported to synthesize a wide range of eicosanoids including prostaglandins, leukotrienes and hydroxyeicosatetraenoic acids (HETEs). Our analysis of arachidonic acid metabolites synthesized by microsomal and cytosolic extracts from adult S. mansoni using thin-layer chromatography and radioimmunoassay techniques indicate the presence of a soluble, enzymatically active lipoxygenase (Lox) and the absence of any cyclooxygenase (Cox) activity. The S. mansoni Lox activity catalyzed the formation of a 15-hydroxyeicosatetraenoic acid (15-HETE)-like species. This activity was calcium-independent and inhibitable by inhibitors of mammalian and plant Lox. The conversion of linoleic acid to a 13-hydroxyoctadecadienoic acid (13-HODE)-like product by S. mansoni extracts indicates that the parasite Lox-homologue is similar to mammalian 15-Lox. Immunoblot analysis of S. mansoni extracts using antisera to different mammalian lipoxygenases detects two immunoreactive proteins with molecular weights similar to plant and mammalian lipoxygenases. In addition, polymerase chain reaction (PCR) amplification of Lox-like sequences from S. mansoni genomic DNA using degenerate primers based on conserved plant and mammalian Lox sequences, generated two PCR products which hybridized to a human 15-Lox cDNA probe. While the role of eicosanoid production in the physiology of S. mansoni is not known, eicosanoids may be essential for normal physiological processes as is the case in other invertebrates. Interestingly, 15-HETE has previously been shown to have immunosuppressive effects in mammals, and this may be related to the ability of the parasite to overcome host immune responses.
此前有报道称曼氏血吸虫能合成多种类二十烷酸，包括前列腺素、白三烯和羟基二十碳四烯酸（HETEs）。我们运用薄层色谱法和放射免疫测定技术，对成年曼氏血吸虫微粒体和胞质提取物合成的花生四烯酸代谢物进行分析，结果表明存在一种可溶性、具有酶活性的脂氧合酶（Lox），且不存在任何环氧化酶（Cox）活性。曼氏血吸虫的Lox活性催化形成一种类似15 - 羟基二十碳四烯酸（15 - HETE）的物质。该活性不依赖于钙，且可被哺乳动物和植物Lox的抑制剂抑制。曼氏血吸虫提取物将亚油酸转化为一种类似13 - 羟基十八碳二烯酸（13 - HODE）的产物，这表明该寄生虫的Lox同源物与哺乳动物的15 - Lox相似。使用针对不同哺乳动物脂氧合酶的抗血清对曼氏血吸虫提取物进行免疫印迹分析，检测到两种免疫反应性蛋白，其分子量与植物和哺乳动物脂氧合酶相似。此外，基于保守的植物和哺乳动物Lox序列，使用简并引物对曼氏血吸虫基因组DNA中的Lox样序列进行聚合酶链反应（PCR）扩增，产生了两个与人类15 - Lox cDNA探针杂交的PCR产物。虽然类二十烷酸的产生在曼氏血吸虫生理学中的作用尚不清楚，但类二十烷酸可能对正常生理过程至关重要，其他无脊椎动物的情况也是如此。有趣的是，此前已表明15 - HETE在哺乳动物中具有免疫抑制作用，这可能与寄生虫克服宿主免疫反应的能力有关。
