Involvement of secretory phospholipase A_2 activity in the zymosan rat air pouch model of inflammation

摘要

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 activity, 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 supernatants of exudates 8 h after injection of zymosan into rat air pouch. This event coincided with peaks in cell accumulation (mainly neutrophils) and myeloperoxidase activity in exudates and was preceded by a rise in eicosanoid levels. 3 This enzyme (without further purification) behaved as a secretory type Ⅱ PLA_2 with an optimum pH at 7-8 units, 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 stimulated myeloperoxidase release in vitro. 5 Injection of the marine PLA_2 inhibitor scalaradial together with zymosan into the pouch at doses of 0.5, 1 and 5 μmol per pouch resulted in a dose-dependent inhibition of PLA_2 activity in exudates collected 8 h later. Myeloperoxidase levels and cell migration were also decreased, while eicosanoid levels 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 released into the exudates. The source of this activity is mainly the neutrophil which migrates into the pouch. 8 Scalaradial exerts anti-inflammatory effects in the zymosan air pouch.