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 Ca 2+ ‐devendent. 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. J. Leukoc. Biol. 56: 644–649; 1994.