Inhibition of phospholipase A(2) as a therapeutic target

The hydrolysis of cell membrane phospholipids by phospholipase A(2) (PLA(2) ) leads to the production of numerous lipid mediators of diverse pathologic al conditions, mainly inflammatory diseases. These include lysophospholipid s and their derivatives, and arachidonic acid and its derivatives (the eico sanoids). Both these groups of mediators are produced predominantly by the secretory PLA(2)s (sPLA(2)s) which hydrolyze the phospholipids of the cell surface membrane. Protection of cell membrane from these 'inflammatory enzy mes' can therefore be used for the treatment of inflammatory processes. A p rototype of cell-impermeable PLA(2) inhibitors, which protect the cell memb rane from different sPLA(2)s without affecting vital phospholipid metabolis m, is presented and discussed in the present review. (C) 2000 Elsevier Scie nce B.V. All rights reserved.