Arch Dermatol Res (1991) 283:77- 80 Archbzes of N@$@81 @B 9 Springer-Verlag1991 Metabolism of exogenous arachidonic acid by polymorphonuclear leukocytes from psoriatic patients J. Solfi 1, L. Vila 1, L. Puig 2, and J. M. de Moragas 2 1 Department of Lipids, Institut de Recerca Biom~dica, and Experimental Dermatology, z Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Aut6noma de Barcelona, Avda. S. Antonio M. Claret 167, E-08025 Barcelona, Spain Received August 30, 1990 Summary. We evaluated the metabolism of exogenous arachidonic acid in polymorphonnclear leukocytes from psoriatic patients in comparison with those from normal subjects. The leukocytes were incubated with 10 ~tM labelled arachidonic acid and 5 ~M A23187 for varying periods of time. We evaluated all the compounds derived from the 5-1ipoxygenase activity, including the products of non-enzymatic transformation of leukotriene A 4 and w- oxidized leukotriene B4. In the experimental conditions used, there was no significant difference in the formation of any compound at any time of incubation. These results indicate that there is no intrinsic alteration either in 5-1ipoxygenase activity or in w-oxidation ability of circulating polymorphonuclear leukocytes in psoriatic patients. Key words: Psoriasis - Arachidonic acid - Eico- sanoids - Polymorphonuclear leukocytes The presence of high concentrations of arachidonic acid (AA) and several eicosanoids in homogenates of psoriatic lesional epidermis was originally described by Hammarstr6m et al. [5]. Since then there have been many reports on AA metabolism in normal and psoriatic skin [1-4, 6, 7, 13]. An important contribution of poly- morphonuclear leukocytes (PMN) to the pool of eicosanoids in psoriatic lessions is suggested by the pres- ence of high concentrations of 5-1ipoxygenase products, mainly leukotriene B, (LTB4). This fact has led several authors [8-10, 12, 15] to investigate possible alterations in AA metabolism by PMN from psoriatic patients. There is some heteroge- neity of results among different studies with regard to 5-1ipoxygenase activity and w-oxidation ability of PMN from psoriatic patients. The previous results provide some contradictory experimental evidence that there may Offprint requests to." L. Vila be differences in AA metabolism between PMN from psoriatic patients and those from controls. Whether these differences are related to 5-1ipoxygenase activity and/or to the catabolism of LTB4 is not yet clear. Total metab- olism of AA through the 5-1ipoxygenase pathway has not been determined in any of these studies. AA is metabolized by PMN 5-1ipoxygenase to 5- HPETE, part of which is reduced to 5-HETE and part converted to LTA4. The latter can undergo enzymatic transformation mainly to LTB4 and to peptido leukotrienes. LTA4 is the common intermediate in leukotriene biosynthesis and can be converted non- enzymatically to the two LTB4 isomers, 5(S),12(R)- dihydroxy-(E,E,E,Z)-6,8,10,14-eicosatetraenoic acid (6- trans-LTB4) and 5(S),12(S)-dihydroxy-(E,E,E,Z)-6,8, 10,14-eicosatetraenoic acid (6-trans- 12-epi-LTB4), and to two epimeric 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acids (5,6-diHETEs) [14]. LTB4 is w-oxidized in PMN to 20-hydroxy- and 20-carboxy-LTB4 (20-OH- and 20- COOH-LTB4) by a 20-hydroxylase [11]. We have carried out a comparative study of AA metabolism in PMN suspensions from a group of eight psoriatic patients and eight normal subjects. Material and methods Patients Peripheral venous blood was taken from eight adult non-diabetic patients (6 male, 2 female, age range 21-64) with chronic stable plaque psoriasis involving more than 10% of the body surface. The patients had not received any kind of treatment for at least 2 weeks. Eight healthy non-smoker adult donors, with an age range and sex distribution similar to those of the psoriatic patients, served as controls. None of the subjects studied was a smoker or had received any medication for 2 weeks prior to blood sample collection. Preparation of P M N suspensions Peripheral venous blood, anticoagulated with ACD-A, was centri- fuged at 200 g for 12 rain at room temperature. The supernatant