Leukotriene B₄‐like material in scale of psoriatic skin lesions

Abstract

Acidic lipid extracts of scale from the lesions of the skin disease, psoriasis, were purified by straight phase high performance liquid chromatography (h.p.l.c). Assay of fractions by an agarose microdroplet chemokinesis method showed the presence of biologically active material that co‐eluted with standard leukotriene B4 (LTB4). LTB4‐like chemokinetic activity was also detected in fractions collected on reversed phase h.p.l.c. of psoriatic scale extracts that were initially purified by straight phase h.p.l.c. No LTB4‐like activity was detected after similar purification of scale obtained by abrasion of large areas of normal skin. The LTB4‐like material found in extracts of psoriatic scale may play a role in the pathogenesis of the neutrophil infiltrate which characterizes psoriasis.

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

“…The observation that NAP/IL-8 is able to activate the neutrophil 5-lipoxygenase might be of biological importance : in psoriasis, a noninfectious skin disease with moderate to severe accumulation of neutrophils in the epidermis, LTB4-like material has been found to be present in elevated amounts (50). 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) .…”

Testing of Lipoxygenase Inhibitors, Cyclooxygenase Inhibitors, Drugs with Immunomodulating Properties and Some Reference Antipsoriatic Drugs in the Modified Mouse Tail Test, an Animal Model of Psoriasis

“…The presence of increased amounts of arachidonic acid derivatives in psoriatic lesions [2,[6][7][8] A decrease in lesional LTB4 [29] was mea sured after local administration of lonapalene whereas no effect on LTB4 was seen after NDGA [26] As in vivo test a modification of the mouse tail test of Jarrett and Spearman was chosen, which measures the induction of a granular layer in the epidermis of adult mouse tails (change of parakeratotic to orthokeratotic dif ferentiation) [21,22], 11 is a physiological model of cell differenti ation without artificial induction, which re presents the defective differentiation (para keratosis, excessive scaling), from which the psoriatic patients seek relief. Drugs with immunomodulating properties were tested in the mouse tail test because of the positive clinical effect of the immunosup pressive drug cyclosporin A (after oral admin istration) on severe psoriatic disease [47], Clinical improvement with corticoids [48] and oral 5-fluorouracil [49] further supported the hypothesis that a dysrégulation of the im mune system might contribute to phenotypic disease, although these drugs also have other characteristics as inhibition of phospholipase A (corticoids) and interference with the thymidylate synthesis (5-fluorouracil).…”

Metabolic disposition of leukotriene B4 (LTB4) and oxidation‐resistant analogues of LTB4 in conscious rabbits

“…In support of its putative role in inflammation, increased local concentrations of LTB4 have been observed in inflammatory conditions, such as purulent peritoneal exudates (Kikawa et al, 1986), inflammatory bowel diseases (Fretland et al, 1990), or psoriatic skin lesions (Brain et al, 1984). Moreover, plasma LTB4 levels may also be transiently elevated, as observed during reperfusion following hindlimb ischaemia in rodents (Goldman et al, 1992) and rabbits (Welbourn et al, 1990), and during anaphylaxis in guinea-pigs (Lee et al, 1986).…”