Proc Natl Acad Sci U S A. 2008 Jan 9 [Epub ahead of print].
"Eoxins are proinflammatory arachidonic acid metabolites produced via the 15-lipoxygenase-1 pathway in human eosinophils and mast cells."
Abstract: Human eosinophils contain abundant amounts of 15-lipoxygenase (LO)-1. The biological role of 15-LO-1 in humans, however, is unclear. Incubation of eosinophils with arachidonic acid led to formation of a product with a UV absorbance maximum at 282 nm and shorter retention time than leukotriene (LT)C(4) in reverse-phase HPLC. Analysis with positive-ion electrospray tandem MS identified this eosinophil metabolite as 14,15-LTC(4). This metabolite could be metabolized to 14,15-LTD(4) and 14,15-LTE(4) in eosinophils. Because eosinophils are such an abundant source of these metabolites and to avoid confusion with 5-LO-derived LTs, we suggest the names eoxin (EX)C(4), -D(4), and -E(4) instead of 14,15-LTC(4), -D(4), and -E(4), respectively. Cord blood-derived mast cells and surgically removed nasal polyps from allergic subjects also produced EXC(4). Incubation of eosinophils with arachidonic acid favored the production of EXC(4), whereas challenge with calcium ionophore led to exclusive formation of LTC(4). Eosinophils produced EXC(4) after challenge with the proinflammatory agents LTC(4), prostaglandin D(2), and IL-5, demonstrating that EXC(4) can be synthesized from the endogenous pool of arachidonic acid. EXs induced increased permeability of endothelial cell monolayer in vitro, indicating that EXs can modulate and enhance vascular permeability, a hallmark of inflammation. In this model system, EXs were 100 times more potent than histamine and almost as potent as LTC(4) and LTD(4). Taken together, this article describes the formation of proinflammatory EXs, in particular in human eosinophils but also in human mast cells and nasal polyps. |
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