ELEVATED EXPRESSION OF HUMAN NONPANCREATIC PHOSPHOLIPASE A(2) IN PSORIATIC TISSUE

In involved psoriatic tissue, which is characterized by chronic inflam mation in both epidermis and dermis, elevated levels of arachidonic ac id and eicosanoids have been measured. This implies that a phospholipa se A(2) (PLA(2)) may be involved in the pathogenesis of psoriasis. The PLA(2)'s are a group of enzymes that release unsaturated fatty acids from the sn2-position of membrane phospholipids. Once released, the fa tty acids are converted by various enzymes into biologically very impo rtant signaling molecules. Release of arachidonate initiates the arach idonate cascade, leading to the synthesis of eicosanoids such as prost aglandins, thromboxanes, leukotrienes, and lipoxines. Eicosanoids are important in a variety of physiological processes and play a central r ole in inflammatory reactions and in intracellular signal transduction processes. Other important inflammatory mediators, such as lyso-PAF ( a precursor for PAF) and other lysophospholipids, may also be formed t hrough the action of a PLA(2). We report for the first time the detect ion of transcripts of nonpancreatic phospholipase A(2) (npPLA(2), type II) and cytosolic (c) PLA(2) in human skin, and overexpression of npP LA(2) in involved skin from patients with psoriasis (plaque psoriasis and pustular psoriasis). Limited amounts of npPLA(2) enzyme are detect ed immunologically in the uppermost layers of epidermis from healthy p ersons. Both involved and uninvolved psoriatic epidermis contain highe r levels of npPLA(2) than normal skin. Positive cells in dermis showed significantly higher levels of npPLA(2) than epidermal cells. In derm is from healthy persons, only weak staining of a few cells could be de tected. The two PLA(2) enzymes detected in psoriatic skin (cytosolic a nd nonpancreatic) may both be involved in eicosanoid overproduction in psoriatic tissue, and the npPLA(2) may also be involved in potentiati ng cell activation, especially T cells.