The metabolism of leukotriene B4 by peripheral blood polymorphonuclear leukocytes in psoriasis.
The formation of leukotriene B4 and its omega-oxidised metabolites has been compared in calcium ionophore-stimulated polymorphonuclear leukocytes, in the absence of exogenous substrate, from fourteen psoriatic subjects and thirteen healthy controls. Although there was no significant difference in the levels of leukotriene B4, the psoriatic cells synthesised significantly greater amounts of omega-oxidation products than control cells. This difference was confirmed in an experiment comparing the time course of formation of the omega-oxidation products of leukotriene B4, under similar conditions, in polymorphonuclear leukocytes from four psoriatic subjects and three healthy controls. The kinetic constants for the metabolism of exogenous leukotriene B4 by 20-hydroxylase were determined by a radiochromatographic enzyme assay in polymorphonuclear leukocytes from three patients with psoriasis and three healthy controls. No significant differences were found in the apparent Km and Vmax values. It is concluded that the increased formation of omega-oxidation products in psoriatic cells may be secondary to increased synthesis of leukotriene B4 by these cells, with consequent increased metabolism, rather than to an inherent abnormality of the 20-hydroxylase system. Further work is needed to determine the kinetics of the enzymes involved in leukotriene B4 synthesis in the psoriatic polymorphonuclear leukocyte, and also to assess the contribution of the leukotriene B4 and omega-oxidation products from polymorphonuclear leukocytes infiltrating the skin to the pathogenesis of the psoriatic lesion.
Maurice
P D
PD
Institute of Dermatology, London, U.K.
Camp
R D
RD
Allen
B R
BR
D000328:Adult; D000001:Calcimycin / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System; D000072470:Cytochrome P450 Family 4; D005260:Female; D006801:Humans; D007700:Kinetics; D007975:Leukotriene B4 / Q000097:blood*; D008297:Male; D006899:Mixed Function Oxygenases / Q000097:blood; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D011565:Psoriasis / Q000097:blood*
D007975:Leukotriene B4; D000001:Calcimycin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D000072470:Cytochrome P450 Family 4; C040780:leukotriene B4 20-hydroxylase