PASTEURELLA-HAEMOLYTICA LEUKOTOXIN-INDUCED SYNTHESIS OF EICOSANOIDS BY BOVINE NEUTROPHILS IN-VITRO

Exposure of isolated bovine neutrophils to partially purified Pasteurella haemolytica leukotoxin caused increased synthesis of leukotriene B-4 (LTB(4)) but not thromboxane B-2 (TXB(2)) from endogenous arachidonic acid. Synthesis of LTB(4) was closely correlated with leukotoxin-induced neutrophil lysis. At low toxin concentrations, LTB(4) production lagged behind leukotoxin-induced neutrophil lysis over a 3-h period. The neutralizing monoclonal antileukotoxin antibody MM601 neutralized both leukotoxin-induced neutrophil lysis and LTB(4) synthesis. Both leukotoxin-induced neutrophil lysis and LTB(4) synthesis were Ca2+-dependent. When leukotoxin-induced LTB(4) synthesis from exogenous arachidonic acid was examined, significant LTB(4) synthesis occurred at 5 min of leukotoxin exposure, which was before leukotoxin-induced lysis developed. Leukotoxin-induced LTB(4) synthesis from endogenous arachidonic acid appears to require leukotoxin-induced plasma membrane damage (occurring during neutrophil lysis), whereas LTB(4) synthesis from exogenous arachidonic acid is initiated rapidly and occurs in the absence of plasma membrane damage.