1. An increase in circulating levels of extracellular group II
phospholipase A2 (PLA2) has been detected in patients with
septic shock as well as in rats, rabbits and human volunteers following intravenous
endotoxin administration. 2. Group II PLA2 from Naja mocambique mocambique (NajaPLA2)
snake venom (1-10 micrograms i.v.) induced a dose-dependent
hypotension and leucopenia in the rat similar to that induced by
intravenous administration of
endotoxin. 3. NajaPLA2 did not aggregate rat platelet, but did aggregate purified rat neutrophils in vitro. However intravenous PLA2 caused rat platelets to aggregate in vivo. 4. The hypotensive effect was reduced either by inactivating NajaPLA2 in vitro with para-
bromophenacyl bromide or by infusing in vivo polyclonal rabbit antiPLA2
antisera. Neither the
hypotension nor the leucopenia was affected by several agonists and inhibitors. 5. The
leukotriene D4 antagonist
L-649,923 produced a dose-related (5-20 mg/kg i.v.) inhibition of NajaPLA2-induced
hypotension while the dual inhibitor of lipo- and
cyclooxygenase BW755c (5-50 mg/kg i.v.) was ineffective. 6. In rats rendered leucopenic with
methotrexate the
L-649,923 was ineffective implying that the
L-649,923 effect could be partially mediated through its action on neutrophils.