Increased concentrations of nonesterified arachidonic acid, 12L-hydroxy-5,8,10,14-eicosatetraenoic acid, prostaglandin E2, and prostaglandin F2alpha in epidermis of psoriasis.

Abstract

Lesional epidermis of psoriasis has a probable reduction in the cyclic AMP/cyclic GMP ratio. This altered ratio may in part be responsible for the characteristic glycogen storage, rapid cell proliferation, and reduced differentiation in lesional epidermis. The concentrations of prostaglandins E2 and F2alpha, free arachidonic acid, and 12L-hydroxy-5,8,10,14-eicosatetrawnoic acid in specimens of uninvolved and involved epidermis of psoriasis were measured with deuterium-labeled carriers and multiple ion analysis. Snap frozen specimens contained: 1.4 +/- 0.4 mug/g (wet weight) of arachidonic acid in uninvolved in contrast to 36.3 +/- 16.7 mug/g in involved epidermis (P = 0.015); less than 0.05 +/- 0.01 mug/g of hydroxyeicosatetraenoic acid in uninvolved in contrast to 4.1 +/- 1.9 mug/g in involved epidermis (P = 0.015); 23.6 +/- 5.0 ng/g of prostaglandin E2 in uninvolved in contrast to 33.1 +/- 5.7 ng/g in involved epidermis (P less than 0.01); and 21.0 +/- 4.4 ng/g of prostaglandin F2alpha in uninvolved in contrast to 39.0 +/- 5.9 ng/g in involved epidermis (P less than 0.01). The arachidonic acid and hydroxyeicosatetraenoic acid levels in involved epidermis were strongly correlated (r = 0.97). The increased levels of arachidonic acid and 12L-hydroxy-5,8,10,14-eicosatetraenoic acid in involved epidermis may have diagnostic and pathophysiological importance.

The monocyte-derived neutrophil activating peptide (NAP/interleukin 8) stimulates human neutrophil arachidonate-5-lipoxygenase, but not the release of cellular arachidonate.

“…In various investigations we were able to show that the major part of neutrophil chemotactic activity in aqueous extracts of lesional psoriatic scales is due to a family of at least seven homologous polypeptides called anionic neutrophil-activating peptide (ANAP) (51), whereby one of the main components, termed N2-ANAP, is by NH2-terminal sequencing, identical with NAPAL-8 (52) . Therefore, it is intriguing to speculate that NAP/IL-8 could be a physiologically relevant activator of PMN-5-lipoxygenase when NAP/IL-8, together with exogenous AA, is present in large amounts in diseased tissue such as in psoriatic lesions (52,53).…”

Prostaglandin Production by Normal and Transformed 3T3 Fibroblasts in Cell Culture

“…Quantitative Analyses of Prostaglandin E2, Prostaglandin F2, and Arachidonic Acid These analyses were performed by quantitative mass spectrometry as described previously for prostaglandins E2 and F l a [18] and for arachidonic acid [19]. Results of prostaglandin analyses were expressed as ng/ml culture medium (cf.…”

“…Diethyl ether in hexane eluted arachidonic acid whereas prostaglandin E2 and prostaglandin F2,, appeared in the combined ethyl acetate and methanol eluates. The compounds were methylated with diazomethane and purified by thin-layer chromatography as described before [19]. Prostaglandin EZ and F2?…”

Contrasting in vitro lymphocyte chemotactic activity of the hydroxyl enantiomers of 12‐hydroxy‐5,8,10,14‐eicosatetraenoic acid

“…The monohydroxy metabolite of arachidonic acid, 8,10,, has been found in elevated levels in samples from lesional psoriatic skin, when compared to those from normal skin (Hammarstrom et al, 1975;Camp et al, 1983) and stereochemical analysis of psoriatic scale-derived 12-HETE has shown that the major stereoisomer present is 12(R)HETE (Woollard, 1986). Analysis of the biological activity of 12(R)-HETE has shown it to be a more potent chemokinetic agent for human neutrophils in vitro than the platelet product, 12(S)-HETE , Cunningham & Woollard, 1987Evans et al, 1987).…”