Chlorinated lipid species in activated human neutrophils: lipid metabolites of 2-chlorohexadecanal.
Neutrophils are important in the host response against invading pathogens. One chemical defense mechanism employed by neutrophils involves the production of myeloperoxidase (MPO)-derived HOCl. 2-Chlorohexadecanal (2-ClHDA) is a naturally occurring lipid product of HOCl targeting the vinyl ether bond of plasmalogens. Previous studies have shown that exogenously-added 2-ClHDA is oxidized to 2-chlorohexadecanoic acid (2-ClHA) and reduced to 2-chlorohexadecanol (2-ClHOH) by endothelial cells. These studies show that both 2-ClHA and 2-ClHOH are produced in activated neutrophils in an MPO- and time-dependent manner and are released by neutrophils into media. 2-ClHDA levels peak following 30 min of phorbol 12-myristate-13-acetate stimulation. In contrast, 2-ClHA and 2-ClHOH levels steadily increased over 60 min, suggesting a precursor-product relationship between 2-ClHDA and both 2-ClHA and 2-ClHOH. Additional experiments using wild-type CHO.K1 and CHO.K1 cells deficient in fatty aldehyde dehydrogenase (FALDH), FAA.K1A, demonstrated that 2-ClHDA oxidation to 2-ClHA is dependent on FALDH activity. Furthermore, mice exposed to intranasal Sendai virus displayed lung neutrophil recruitment, as well as elevated 2-ClHA levels in plasma and bronchoalveolar lavage compared with control-treated mice. Taken together, these data demonstrate, for the first time, that metabolites of 2-ClHDA are produced both in vivo as well as in isolated human neutrophils.
Anbukumar
Dhanalakshmi S
DS
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Shornick
Laurie P
LP
Albert
Carolyn J
CJ
Steward
Melissa M
MM
Zoeller
Raphael A
RA
Neumann
William L
WL
Ford
David A
DA
D000447:Aldehydes / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D018893:Bronchoalveolar Lavage; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005233:Fatty Alcohols / Q000378:metabolism; D054879:Halogenation; D006801:Humans; D050356:Lipid Metabolism / Q000276:immunology*; D051379:Mice; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D012141:Respiratory Tract Infections / Q000276:immunology / Q000821:virology
C432398:2-chlorohexadecanal; D000447:Aldehydes; D005233:Fatty Alcohols; D010703:Phorbol Esters; C005031:cetyl alcohol