Recombinant bovine interleukin-1 beta amplifies the effects of partially purified Pasteurella haemolytica leukotoxin on bovine neutrophils in a beta(2)-integrin-dependent manner

The influx and death of polymorphonuclear leukocytes within the infected lu ng are hallmarks of bovine pasteurellosis. Recent reports have shown that t he Pasteurella haemolytica leukotoxin (LKT) and other RTX toxins bind beta( 2)-integrins on target cells. In this study we demonstrate that exposure of bovine neutrophils to recombinant bovine interleukin-1 beta upregulates be ta(2)-integrins (CD11a/CD18), which in turn enhance the binding and amplify the biological effects of partially purified LKT on these cells. LKT bindi ng and cytotoxicity were inhibited by addition of an anti-integrin antibody (CD11a/CD18). These findings help to clarify the early events that occur i n bovine pasteurellosis and support the hypothesis that inflammatory mediat ors might increase the severity of pasteurellosis by causing upregulation o f beta(2)-integrins that serve as an LKT receptor on bovine neutrophils.