Reactive chlorinating species produced during neutrophil activation target tissue plasmalogens: production of the chemoattractant, 2-chlorohexadecanal.
Recently alpha-chloro fatty aldehydes have been shown to be products of reactive chlorinating species targeting the vinyl ether bond of plasmalogens utilizing a cell-free system. Accordingly, the present experiments were designed to show that alpha-chloro fatty aldehydes are produced by activated neutrophils and to determine their physiologic effects. A sensitive gas chromatography-mass spectrometry technique was developed to detect pentafluorobenzyl oximes of alpha-chloro fatty aldehydes utilizing negative ion chemical ionization. Phorbol 12-myristate 13-acetate activation of neutrophils resulted in the production of both 2-chlorohexadecanal and 2- chlorooctadecanal through a myeloperoxidase-dependent mechanism that likely involved the targeting of both 16 and 18 carbon vinyl ether-linked aliphatic groups present in the sn-1 position of neutrophil plasmalogens. 2-Chlorohexadecanal was also produced by fMLP-treated neutrophils. Additionally, reactive chlorinating species released from activated neutrophils targeted endothelial cell plasmalogens resulting in 2-chlorohexadecanal production. Physiologically relevant concentrations of 2-chlorohexadecanal induced neutrophil chemotaxis in vitro suggesting that alpha-chloro fatty aldehydes may have a role in neutrophil recruitment. Taken together, these studies demonstrate for the first time a novel biochemical mechanism that targets the vinyl ether bond of plasmalogens during neutrophil activation resulting in the production of alpha-chloro fatty aldehydes that may enhance the recruitment of neutrophils to areas of active inflammation.
Thukkani
Arun K
AK
Department of Biochemistry, St. Louis University Health Sciences Center, St. Louis, Missouri 63104, USA.
Hsu
Fong-Fu
FF
Crowley
Jan R
JR
Wysolmerski
Robert B
RB
Albert
Carolyn J
CJ
Ford
David A
DA
D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002713:Chlorine / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D018375:Neutrophil Activation; D010955:Plasmalogens / Q000378:metabolism*
C432398:2-chlorohexadecanal; D000447:Aldehydes; D010955:Plasmalogens; D002713:Chlorine