Eosinophil peroxidase-derived reactive brominating species target the vinyl ether bond of plasmalogens generating a novel chemoattractant, alpha-bromo fatty aldehyde.
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.
Albert
Carolyn J
CJ
Department of Biochemistry, St. Louis University Health Sciences Center, St. Louis, Missouri 63104, USA.
Thukkani
Arun K
AK
Heuertz
Rita M
RM
Slungaard
Arne
A
Hazen
Stanley L
SL
Ford
David A
DA
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000494:pharmacology; D000447:Aldehydes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001671:Biochemistry / Q000379:methods; D001965:Bromides / Q000494:pharmacology; D001966:Bromine / Q000737:chemistry; D002630:Chemotactic Factors / Q000494:pharmacology; D002845:Chromatography; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000201:enzymology; D004987:Ethers / Q000737:chemistry*; D005464:Fluorobenzenes / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry; D008244:Lysophosphatidylcholines / Q000737:chemistry; D013058:Mass Spectrometry; D008956:Models, Chemical; D009504:Neutrophils / Q000201:enzymology; D010544:Peroxidases / Q000378:metabolism*; D010586:Phagocytes; D010955:Plasmalogens / Q000737:chemistry* / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D017670:Sodium Compounds / Q000494:pharmacology; D013552:Swine; D005466:Fluorocarbons
D000079:Acetaldehyde; D000447:Aldehydes; D001965:Bromides; D001966:Bromine; D002630:Chemotactic Factors; D004791:Enzyme Inhibitors; D047209:Eosinophil Peroxidase; D004987:Ethers; D005464:Fluorobenzenes; D008055:Lipids; D008244:Lysophosphatidylcholines; D010544:Peroxidases; D010955:Plasmalogens; D012965:Sodium Chloride; D017670:Sodium Compounds; C473768:2-bromohexadecanal; C032459:choline plasmalogens; C052470:acetaldehyde-O-pentafluorobenzyloxime; D005466:Fluorocarbons; C027938:sodium bromide; C001647:hexadecanal