In vitro synthesis of 12-hydroxy-eicosatetraenoic acid is increased in uninvolved psoriatic epidermis

Abstract

Certain arachidonic acid (AA) metabolites have been detected in psoriatic skin lesions. In this study the capacity of normal epidermis and clinically uninvolved psoriatic epidermis to transform AA into lipoxygenase products was determined in vitro. After incubating homogenized epidermis with exogenous AA, the extracted lipids were isolated by reverse-phase high-performance liquid chromatography. Each chromatographic peak was characterized by its UV absorption spectrum and identified by its coelution with the appropriate authentic standard and by radioimmunoassay of its eluate fraction. Identified compounds were quantitated by integrated UV absorbance. Leukotriene B4 (LTB4) was also identified by neutrophil chemokinesis. Normal epidermis generated 15-hydroxy-eicosatetraenoic acid (15-HETE) and 12-HETE, the latter being more abundant. 5-Lipoxygenase products (LTB4, LTC4, and 5-HETE) were not detected. However, an unknown compound exhibiting a triplet UV absorbtion spectrum with maximum at 274 mm was formed. Its formation was inhibited by 5,8,11,14-eicosatetraynoic acid, but not by indomethacin or a specific 5-lipoxygenase inhibitor (REV 5901). These data suggest that a di-HETE with a triene structure is one possible candidate for the unknown compound. Compared with normal epidermis, the formation of 12-HETE and the unknown di-HETE by uninvolved psoriatic epidermis was increased by 54% and 63%, respectively. The formation of 12-HETE and the unknown di-HETE in uninvolved psoriatic epidermis was stimulated to the same degree in the presence of the phospholipase inhibitor quinacrine. These results indicate that uninvolved psoriatic epidermis has an increased capacity to metabolize free AA into 12-lipoxygenase products.