PANCREATIC-TYPE PHOSPHOLIPASE A(2) INDUCES GROUP-II PHOSPHOLIPASE A(2) EXPRESSION AND PROSTAGLANDIN BIOSYNTHESIS IN RAT MESANGIAL CELLS

The effect of pancreatic group I phospholipase Az (PLA(2)-I) on recept or-mediated expression of arthritic group II phospholipase A(2) (PLA(2 )-II) and its correlation with prostaglandin E(2) (PGE(2)) synthesis w ere examined in cultured rat mesangial cells. Scatchard analysis using I-125-PLA(2)-I revealed the existence of a single class of specific b inding sites for PLA(2)-I in rat mesangial cells with an equilibrium d issociation constant (K-d) of 1.6 nM and a maximum binding capacity of 10.1 fmol/10(6) cells. The mammalian mature type of PLA(2)-I specific ally recognized this binding site, whereas its inactive zymogen and ma mmalian PLA(2)-II showed much lower affinities. PLA(2)-I markedly incr eased PLA(2)-II mRNA levels as well as PLA(2)-II secretion from the ce lls in a time- and dose-dependent manner that was closely correlated w ith PGE(2) production. Both PLA(2)-II expression and PGE(2) synthesis were completely suppressed by pretreatment of the cells with actinomyc in D, cycloheximide, or dexamethasone. These results strongly suggest that there may be crosstalk between PLA(2)-I and PLA(2)-II via the spe cific PLA(2)-I receptor that elicits PGE(2) synthesis.