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 β subunit of β2-integrins, mediates Lkt-induced cytolysis. However, it is not clear whether CD18 of all three β2-integrins, LFA-1, Mac-1, and CR4, mediates Lkt-induced cytol-ysis. 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 intracellular 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.
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1 July 2008
Bighorn Sheep β2-Integrin LFA-1 Serves as a Receptor for Mannheimia haemolytica Leukotoxin
Rohana P. Dassanayake,
Weiguo Liu,
William C. Davis,
William J. Foreyt,
Subramaniam Srikumaran
Journal of Wildlife Diseases
Vol. 44 • No. 3
July 2008
Vol. 44 • No. 3
July 2008
Bighorn Sheep
leukotoxin
LFA-1
Mannheimia haemolytica
receptor