title: Bighorn sheep beta2-integrin LFA-1 serves as a receptor for Mannheimia haemolytica leukotoxin.
abstract: Mannheimia haemolytica is an important cause of pneumonia in bighorn sheep (BHS; Ovis canadensis). Leukotoxin (Lkt), the primary virulence determinant of M. haemolytica, induces cytolysis of all subsets of leukocytes. Previously, we have shown that CD18, the beta subunit of beta2-integrins, mediates Lkt-induced cytolysis. However, it is not clear whether CD18 of all three beta2-integrins, LFA-1, Mac-1, and CR4, mediates Lkt-induced cytolysis. The objective of this study was to determine whether BHS LFA-1 (CD11a/CD18) serves as a receptor for Lkt. Plasmids encoding cDNA for BHS CD11a and CD18 were cotransfected into Lkt-resistant HEK-293 cells. Flow cytometric analysis of transfectants confirmed cell surface expression of BHS LFA- 1, Lkt-LFA-1 binding and Lkt-induced intra-cellular calcium elevation. More importantly, the transfectants were efficiently lysed by Lkt in a concentration-dependent manner. Collectively, these results indicate that BHS LFA-1 serves as a functional receptor for M. haemolytica Lkt.
authors.affiliation: Department of Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA.
authors.forename: Rohana P
authors.initials: RP
authors.lastname: Dassanayake
authors.forename: Weiguo
authors.initials: W
authors.lastname: Liu
authors.forename: William C
authors.initials: WC
authors.lastname: Davis
authors.forename: William J
authors.initials: WJ
authors.lastname: Foreyt
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Srikumaran
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000276:immunology*; D005098:Exotoxins / Q000096:biosynthesis* / Q000378:metabolism; D005434:Flow Cytometry / Q000662:veterinary; D007962:Leukocytes / Q000378:metabolism; D016978:Mannheimia haemolytica / Q000276:immunology / Q000378:metabolism*; D012766:Pasteurellosis, Pneumonic / Q000276:immunology* / Q000382:microbiology; D016028:Receptors, Leukocyte-Adhesion / Q000378:metabolism; D012756:Sheep; D012757:Sheep Diseases / Q000276:immunology* / Q000382:microbiology; D034581:Sheep, Bighorn; D014162:Transfection / Q000662:veterinary
chemical_list: D018821:CD18 Antigens; D005098:Exotoxins; D016028:Receptors, Leukocyte-Adhesion; C018579:leukotoxin