Role of intracellular calcium in Pasteurella haemolytica leukotoxin-induced bovine neutrophil leukotriene B-4 production and plasma membrane damage

Isolated neutrophils were used to study the intracellular calcium ([Ca2+](i )) dependency of Pasteurella haemolytica leukotoxin-induced production of l eukotriene B-4 and plasma membrane damage. Exposure of neutrophils to leuko toxin caused a rapid and concentration-dependent increase in [Ca2+](i), fol lowed by simultaneous plasma membrane damage and production of leukotriene B-4. Removal of extracellular Ca2+, replacement of Ca2+ with other divalent cations, or exposure to high concentration of verapamil, an inhibitor of v oltage-dependent calcium channels, inhibited leukotoxin-induced increases i n [Ca2+](i), leukotriene B-4 production, and membrane damage, thus indicati ng that influx of extracellular Ca2+ is necessary to produce these leukotox in-induced neutrophil responses. (C) 1999 Published by Elsevier Science B.V . All rights reserved.