INVOLVEMENT OF SECRETORY PHOSPHOLIPASE A(2) ACTIVITY IN THE ZYMOSAN RAT AIR POUCH MODEL OF INFLAMMATION

1 In the zymosan rat air pouch model of inflammation we have assessed the time dependence of phospholipase A(2) (PLA(2)) accumulation in the inflammatory exudates as well as cell migration, myeloperoxidase acti vity, prostaglandin E(2) (PGE(2)) and leukotriene B-4 (LTB(4)) levels. 2 A significant increase in PLA(2) activity was detected in 1,200 g s upernatants of exudates 8 h after injection of zymosan into rat air po uch. This event coincided with peaks in cell accumulation (mainly neut rophils) and myeloperoxidase activity in exudates and was preceded by a rise in eicosanoid levels. 3 This enzyme (without further purificati on) behaved as a secretory type II PLA(2) with an optimum pH at 7-8 un its, lack of selectivity for arachidonate release and dependence on mM calcium concentrations for maximal activity. 4 The PLA(2) inhibitors manoalide and scalaradial inhibited this enzyme activity in vitro in a concentration-dependent manner. Scalaradial also inhibited zymosan st imulated myeloperoxidase release in vitro. 5 Injection of the marine P LA(2) inhibitor scalaradial together with zymosan into the pouch at do ses of 0.5, 1 and 5 mu mol per pouch resulted in a dose-dependent inhi bition of PLA(2) activity in exudates collected 8 h later. Myeloperoxi dase levels and cell migration were also decreased, while eicosanoid l evels were not modified. 6 Colchicine administration to rats prevented infiltration and decreased PLA(2) levels in the 8 h zymosan-injected air pouch. 7 These results indicate that during inflammatory response to zymosan in the rat air pouch a secretory PLA(2) activity is release d into the exudates. The source of this activity is mainly the neutrop hil which migrates into the pouch. 8 Scalaradial exerts anti-inflammat ory effects in the zymosan air pouch.