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¹ Department of Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA
² Corresponding author (email: ssrikumaran{at}vetmed.wsu.edu)

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 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 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.
  Key words:  Bighorn sheep, leukotoxin, LFA-1, Mannheimia haemolytica, receptor.