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

In involved psoriatic tissue, which is characterized by chronic inflammation in both epidermis and dermis, elevated levels of arachidonic acid and eicosanoids have been measured. This implies that a phospholipase 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 fatty acids are converted by various enzymes into biologically very important signaling molecules. Release of arachidonate initiates the arachidonate cascade, leading to the synthesis of eicosanoids such as prostaglandins, thromboxanes, leukotrienes, and lipoxines. Eicosanoids are important in a variety of physiological processes and play a central role 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 through the action of a PLA(2). We report for the first time the detection of transcripts of nonpancreatic phospholipase A(2) (npPLA(2), type II) and cytosolic (c) PLA(2) in human skin, and overexpression of npPLA(2) in involved skin from patients with psoriasis (plaque psoriasis and pustular psoriasis). Limited amounts of npPLA(2) enzyme are detected immunologically in the uppermost layers of epidermis from healthy persons. Both involved and uninvolved psoriatic epidermis contain higher levels of npPLA(2) than normal skin. Positive cells in dermis showed significantly higher levels of npPLA(2) than epidermal cells. In dermis from healthy persons, only weak staining of a few cells could be detected. The two PLA(2) enzymes detected in psoriatic skin (cytosolic and nonpancreatic) may both be involved in eicosanoid overproduction in psoriatic tissue, and the npPLA(2) may also be involved in potentiating cell activation, especially T cells.