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.