February 2010

[JLR] Chlorine Keeps It Clean

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Temporal course of 2-ClHDA, 2-ClHOH and 2-ClHA production in stimulated human neutrophils.

Neutrophils are an abundant component of the innate immune system that attack pathogens by releasing chemical agents such as hydrogen peroxide and hypochlorous acid. However, these agents also can attack host macromolecules to form reactive species, such as chlorinated lipids. In this study, the authors traced the metabolic fate of two such metabolites: 2-chlorohexadecanoic acid and 2-chlorohexadecanol. Using isolated neutrophils, they demonstrated that both 2-ClHA and 2-ClHOH are produced and released in activated neutrophils in a time- and myeloperoxidase-dependent manner. (Myeloperoxidase catalyzes HOCl production.) Oxidation of 2-ClHDA to 2-ClHA also was dependent on the enzyme fatty aldehyde dehydrogenase. The authors confirmed these events in a physiological context, showing that mice exposed to intranasal Sendai virus experienced an increased recruitment of neutrophils to the lungs, followed by elevated ClHA levels in both plasma and bronchoalveolar lavage compared with control-treated mice. Thus, they demonstrated for the first time that chlorinated lipid metabolites are produced by neutrophils in vivo.

Chlorinated Lipid Species in Activated Human Neutrophils: Lipid Metabolites of 2-Chlorohexadecanal 

Dhanalakshmi S. Anbukumar, Laurie P. Shornick, Carolyn J. Albert, Melissa M. Steward, Raphael A. Zoeller, William L. Neumann and David A. Ford

J. Lipid Res., published online Dec. 17, 2009 


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