PLATELET-ACTIVATING-FACTOR, LYSO-PLATELET-ACTIVATING-FACTOR AND ARACHIDONIC-ACID RELEASE IN NORMAL HUMAN SKIN AND THE INFLUENCE OF TOPICAL STEROID TREATMENT

1 Previous, in vitro, studies have established the synthesis of platel et activating factor (PAF) by the 're-modelling' pathways in which the activation of a phospholipase A2 (PLA2) enzyme catalyses the hydrolys is of an ether-acyl-phosphocholine to give concomitant release of lyso -PAF, the immediate precursor of PAF, and arachidonic acid, the precur sor of the eicosanoids. The aim of this study was to investigate the r elationship between PAF and eicosanoid release in human skin, and to s tudy the effect of treatment of skin with a topical steroid, on the re lease of PAF, lyso-PAF and arachidonic acid. 2 A novel assay procedure was developed for the simultaneous assay of PAF and lyso-PAF in skin exudates from abrasions and suction blisters in normal human skin. In addition we assayed arachidonic acid and prostaglandin E2 (PGE2), a re presentative eicosanoid. 3 The mean amounts of mediator recovered in t he first 30 min period following abrasion were PAF 0.43, lyso-PAF 11.9 , PGE2 25.7 and arachidonic acid 760 pmol/sample. The molar ratio of P AF:lyso-PAF: arachidonic acid in skin exudates from abrasions was 1:30 :1800 and in suction blister exudates was 1:90:3660. 4 Time course stu dies showed a decline in the recoveries of arachidonic acid and lyso-P AF, of about 50% in 2 h. In contrast, PAF was recovered in exudates at a constant rate over 2 h but PGE2 release decreased by more than 90% after the initial 30 min period. 5 Topical application under occlusion , of 0.05% clobetasol propionate, a potent corticosteroid, significant ly reduced lyso-PAF by 30% in suction blister exudates but did not sig nificantly alter the concentrations of PAF or arachidonic acid. 6 Thes e results show that, in normal human skin, the recovered quantitites o f PAF, lyso-PAF and the eicosanoids do not demonstrate a common metabo lic pathway for their production. Although corticosteroid treatment re duced lyso-PAF the reduction was not sufficient to affect levels of PA F in skin.