Eosinophil Peroxidase-derived Reactive Brominating Species Target the Vinyl Ether Bond of Plasmalogens Generating a Novel Chemoattractant, α-Bromo Fatty Aldehyde

Abstract

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 M 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.

Eosinophil Cysteinyl Leukotriene Synthesis Mediated by Exogenous Secreted Phospholipase A2 Group X

“…We found that sPLA 2 -X causes marked lysophospholipid release from eosinophils, including marked release of LysoPC species known to induce a Ca 2ϩ flux in eosinophils. A full analysis of the lysophospholipid species established that free fatty acids are predominantly released from species enriched in AA in human eosinophils, including phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine (37) as well as plasmenyl phosphatidylcholine and phosphatidylethanolamine species (38). We determined that sPLA 2 -X-mediated CysLT synthesis but not AA release could be suppressed by inhibition of cPLA 2 ␣, suggesting that sPLA 2 -X activates cPLA 2 ␣.…”

Bromofatty aldehyde derived from bromine exposure and myeloperoxidase and eosinophil peroxidase modify GSH and protein

“…Previous studies have shown α-BrFALD is produced in human neutrophils and eosinophils (2,11). Since bromine is a better leaving group than chlorine, it was anticipated that α-BrFALD would react with GSH through a thiol-dependent mechanism similar to that of α-ClFALD with GSH (12).…”

In vitro toxicity evaluation of diesel exhaust particles on human eosinophilic cell

“…In addition, it is known that eosinophils which infiltrate the site of inflammation have in their cells a major basic protein that has cytotoxic properties. By releasing cytokines (Schmid-Grendelmeier et al, 2002), lipid mediators (Busse, 1998), reactive oxygen species (Albert et al, 2003), and highly charged cytotoxic granular proteins (Marguet et al, 2001), activated eosinophils contribute to airway inflammation and cause damage of the bronchial mucosa (Pegorier et al, 2006). Therefore, today eosinophils are thought to play a central role in enhancing inflammation.…”