More bad news for the "essential fatty acid" crowd - will they ever learn?
- From: monty1945@xxxxxxxxx
- Date: Fri, 11 Jan 2008 19:53:02 -0800 (PST)
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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