Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: October 13, 1996
Publication Date: N/A
The relevance of leukotoxin (Lkt) in the pathogenesis of lung injury in bovine pneumonia pasteurellosis was first established in calf models with the use of log phase Pasteurella haemolytica A1 as challenge organisms. We demonstrated that the severity of the clinical and pathological hallmark lesions seen in the disease positively correlated with the concentration of Lkt secreted by the challenge organism. In this model, Lkt was present in the alveolar inflammatory exudate specifically bound to the membranes of degenerating AMs and PMNs but not in the parenchyma cells. These effects were not observed when a knockout mutant of P. haemolytica (Ikt A77 strain) which does not synthesize Lkt was used as the challenge organism. The Lkt also possess an impressive spectrum of biological activities. In particular, the toxic oxygen radicals and proteases released from Lkt-stimulated alveolar neutrophils can degrade components of the lung and contribute to neutrophil-mediated endothelial damage. We have since described a procedure to obtain biologically active Lkt free LPS and demonstrated that the highly purified Lkt induced expression of inflammatory cytokines (TNF alpha particle, IL-1beta, and IL-8), and nitric oxide from alveolar macrophages. Results from two separate studies using a vaccination-challenge model in cattle suggest that vaccines which induced high levels of anti-Lkt antibodies provided the greatest protective immunity.