title: Prior exposure to Mannheimia haemolytica leukotoxin or LPS enhances beta(2)-integrin expression by bovine neutrophils and augments LKT cytotoxicity.
abstract: Mannheimia (Pasteurella) haemolytica serotype1 produces a variety of virulence factors that play an important role during the pathogenesis of bovine pneumonic pasteurellosis. Among these, a leukotoxin (LKT) and lipopolysaccharide (LPS) are thought to be the primary virulence factors that contribute to the characteristic pathology of pasteurellosis. Recent evidence suggests that M. haemolytica LKT binding to bovine leukocytes is mediated by the beta(2)-integrin CD11a/CD18 (LFA-1), which subsequently induces activation and death of these cells. Exposure of bovine peripheral blood neutrophils (PMNs) to LKT or LPS induces expression of inflammatory cytokines, which in turn can increase LFA-1 expression and conformational activation. In this study we demonstrated, by flow cytometry and Western blot, that bovine PMNs increased their LFA-1 expression following in vitro exposure to M. haemolytica LKT and LPS. Increased LFA-1 expression by PMNs exposed to LKT and LPS was associated with increased LKT binding and cell death. The results of this study suggest that M. haemolytica LKT and LPS might cooperatively increase LFA-1 expression, and by so doing amplify the lung inflammation that characterizes bovine pasteurellosis.
authors.affiliation: Department of Pathological Sciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive West, Madison, WI 53705, USA.
authors.forename: F
authors.initials: F
authors.lastname: Leite
authors.forename: S
authors.initials: S
authors.lastname: Gyles
authors.forename: D
authors.initials: D
authors.lastname: Atapattu
authors.forename: S K
authors.initials: SK
authors.lastname: Maheswaran
authors.forename: C J
authors.initials: CJ
authors.lastname: Czuprynski
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis; D001427:Bacterial Toxins / Q000633:toxicity*; D001665:Binding Sites; D015153:Blotting, Western / Q000379:methods; D018821:CD18 Antigens / Q000096:biosynthesis* / Q000378:metabolism; D002417:Cattle; D003603:Cytotoxins / Q000633:toxicity; D005098:Exotoxins / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000633:toxicity*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D016978:Mannheimia haemolytica / Q000472:pathogenicity*; D009154:Mutation; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D018821:CD18 Antigens; D003603:Cytotoxins; D005098:Exotoxins; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; C018579:leukotoxin