Albert Carolyn J, Thukkani Arun K, Heuertz Rita M, Slungaard Arne, Hazen Stanley L, Ford David A
Department of Biochemistry, St. Louis University Health Sciences Center, St. Louis, Missouri 63104, USA.
J Biol Chem. 2003 Mar 14;278(11):8942-50. doi: 10.1074/jbc.m211634200.
Plasmalogens are a subclass of glycerophospholipids that are enriched in the plasma membrane of many mammalian cells. The vinyl ether bond of plasmalogens renders them susceptible to oxidation. Accordingly, it was hypothesized that reactive brominating species, a unique oxidant formed at the sites of eosinophil activation, such as in asthma, might selectively target plasmalogens for oxidation. Here we show that reactive brominating species produced by the eosinophil peroxidase system of activated eosinophils attack the vinyl ether bond of plasmalogens. Reactive brominating species produced by eosinophil peroxidase target the vinyl ether bond of plasmalogens resulting in the production of a neutral lipid and lysophosphatidylcholine. Chromatographic and mass spectrometric analyses of this neutral lipid demonstrated that it was 2-bromohexadecanal (2-BrHDA). Reactive brominating species produced by eosinophil peroxidase attacked the plasmalogen vinyl ether bond at acidic pH. Bromide was the preferred substrate for eosinophil peroxidase, and chloride was not appreciably used even at a 1000-fold molar excess. Furthermore, 2-BrHDA production elicited by eosinophil peroxidase-derived reactive brominating species in the presence of 100 microM NaBr doubled with the addition of 100 mM NaCl. The potential physiological significance of this pathway was suggested by the demonstration that 2-BrHDA was produced by phorbol myristate acetate-stimulated eosinophils and by the demonstration that 2-BrHDA is a phagocyte chemoattractant. Taken together, the present studies demonstrate the targeting of the vinyl ether bond of plasmalogens by the reactive brominating species produced by eosinophil peroxidase and by activated eosinophils, resulting in the production of brominated fatty aldehydes.
缩醛磷脂是甘油磷脂的一个亚类，在许多哺乳动物细胞的质膜中含量丰富。缩醛磷脂的乙烯基醚键使其易于氧化。因此，有人推测，反应性溴化物质是在嗜酸性粒细胞活化部位（如哮喘中）形成的一种独特氧化剂，可能会选择性地靶向缩醛磷脂进行氧化。在这里，我们表明活化嗜酸性粒细胞的嗜酸性粒细胞过氧化物酶系统产生的反应性溴化物质会攻击缩醛磷脂的乙烯基醚键。嗜酸性粒细胞过氧化物酶产生的反应性溴化物质靶向缩醛磷脂的乙烯基醚键，导致产生一种中性脂质和溶血磷脂酰胆碱。对这种中性脂质的色谱和质谱分析表明它是2-溴十六醛（2-BrHDA）。嗜酸性粒细胞过氧化物酶产生的反应性溴化物质在酸性pH下攻击缩醛磷脂的乙烯基醚键。溴化物是嗜酸性粒细胞过氧化物酶的首选底物，即使氯化物的摩尔过量1000倍也不会被明显利用。此外，在100 microM NaBr存在下，嗜酸性粒细胞过氧化物酶衍生的反应性溴化物质引发的2-BrHDA生成在添加100 mM NaCl后增加了一倍。佛波酯刺激的嗜酸性粒细胞产生2-BrHDA以及2-BrHDA是吞噬细胞趋化剂的证明表明了该途径潜在的生理意义。综上所述，本研究证明了嗜酸性粒细胞过氧化物酶和活化的嗜酸性粒细胞产生的反应性溴化物质靶向缩醛磷脂的乙烯基醚键，导致产生溴化脂肪醛。
