thromboxane-b2 and leukotoxin

To identify the effect of Pasteurella haemolytica lipopolysaccharide (LPS) and leukotoxin (LKT) on spontaneous and calcium ionophore-induced histamine and inflammatory mediator release from isolated bovine lung parenchyma.. Lungs from 8 healthy cattle.. Isolated bovine lung parenchyma was incubated in vitro for 2 hours with LKT or LPS, and spontaneous and induced release of inflammatory mediators was determined.. LKT and LPS increased spontaneous release of histamine and leukotriene B4. In addition, incubation with LPS increased spontaneous release of prostaglandin E2. Moreover, a differential effect of the 2 toxins on calcium ionophore-induced inflammatory mediator release was observed. LKT specifically primed isolated lung parenchyma to release leukotriene B4 and thromboxane B2 in response to calcium ionophore, whereas LPS did not alter the profile of prostanoids released by bovine lung tissue exposed to calcium ionophore.. Pasteurella haemolytica toxins have a direct effect on bovine lung parenchyma, causing release of inflammatory mediators, which contribute to response to infection. Furthermore, bacterial toxins (LKT in this study) may sensitize tissues to the effects of other irritant stimuli, amplifying the inflammatory response.

Topics: Animals; Bacterial Toxins; Cattle; Dinoprostone; Eicosanoids; Exotoxins; Histamine; Ionophores; Leukotriene B4; Lipopolysaccharides; Lung; Mannheimia haemolytica; Organ Culture Techniques; Thromboxane B2; Time Factors

Exposure of isolated bovine neutrophils to partially purified Pasteurella haemolytica leukotoxin caused increased synthesis of leukotriene B4 (LTB4) but not thromboxane B2 (TXB2) from endogenous arachidonic acid. Synthesis of LTB4 was closely correlated with leukotoxin-induced neutrophil lysis. At low toxin concentrations, LTB4 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 LTB4 synthesis. Both leukotoxin-induced neutrophil lysis and LTB4 synthesis were Ca(2+)-dependent. When leukotoxin-induced LTB4 synthesis from exogenous arachidonic acid was examined, significant LTB4 synthesis occurred at 5 min of leukotoxin exposure, which was before leukotoxin-induced lysis developed. Leukotoxin-induced LTB4 synthesis from endogenous arachidonic acid appears to require leukotoxin-induced plasma membrane damage (occurring during neutrophil lysis), whereas LTB4 synthesis from exogenous arachidonic acid is initiated rapidly and occurs in the absence of plasma membrane damage.

Topics: Animals; Cattle; Cells, Cultured; Cytotoxins; Exotoxins; Leukotriene B4; Mannheimia haemolytica; Neutrophils; Thromboxane B2