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Journal of Wildlife Diseases, 43(1), 2007, pp. 75-81
© Wildlife Disease Association  2007
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MANNHEIMIA (PASTEURELLA) HAEMOLYTICA LEUKOTOXIN UTILIZES CD18 AS ITS RECEPTOR ON BIGHORN SHEEP LEUKOCYTES

 Weiguo Liu1, Kelly A. Brayton1, William C. Davis1, Kristin Mansfield2, John Lagerquist1, William Foreyt1 and Subramaniam Srikumaran1,3

1 Department of Microbiology and Pathology, Washington State University, Pullman, Washington 99164-7040, USA
2 Washington Department of Fish and Wildlife, Spokane Valley, Washington 99216-1566, USA
3 Corresponding author (email: ssrikumaran{at}vetmed.wsu.edu)

ABSTRACT:   Pneumonia caused by Mannheimia (Pasteurella) haemolytica is a highly fatal disease of bighorn sheep (Ovis canadensis). Leukotoxin (Lkt), secreted by M. haemolytica, is an important virulence factor of this organism, and is cytolytic to bighorn sheep leukocytes. Previously, we have shown that CD18, the ß subunit of ß2 integrins, serves as the receptor for Lkt on bovine leukocytes. Furthermore, anti-CD18 antibodies inhibit Lkt-induced cytotoxicity of bighorn sheep leukocytes. Therefore, we hypothesized that Lkt utilizes CD18 as its receptor on bighorn sheep leukocytes. Confirmation of bighorn sheep CD18 as a receptor for Lkt requires the demonstration that the recombinant expression of bighorn sheep CD18 in Lkt-nonsusceptible cells renders them susceptible to Lkt. Therefore, we transfected cDNA encoding CD18 of bighorn sheep into a Lkt-nonsusceptible murine cell line. Cell surface expression of bighorn sheep CD18 on the transfectants was tested by flow cytometry with anti-CD18 antibodies. Transfectants stably expressing bighorn sheep CD18 on their surface were subjected to flow cytometric analysis for detection of Lkt binding, and cytotoxicity assays for detection of Lkt-induced cytotoxicity. Leukotoxin bound to the transfectants. More importantly, the transfectants were effectively lysed by Lkt in a concentration-dependent manner, whereas the parent cells were not. These results clearly indicate that M. haemolytica Lkt utilizes CD18 as a receptor on bighorn sheep leukocytes. Identification of CD18 as a receptor for Lkt on bighorn sheep leukocytes should enhance our understanding of the pathogenesis of pneumonia, which in turn should help in the development of control measures against this fatal disease of bighorn sheep.
  Key words:  Bighorn sheep, CD18, leukotoxin, Mannheimia (Pasteurella) haemolytica, Ovis canadensis, receptor.




This article has been cited by other articles:


Home page
 J Wildl DisHome page
R. P. Dassanayake, W. Liu, W. C. Davis, W. J. Foreyt, and S. Srikumaran
Bighorn Sheep {beta}2-Integrin LFA-1 Serves as a Receptor for Mannheimia haemolytica Leukotoxin
J. Wildl. Dis., July 1, 2008; 44(3): 743 - 747.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
R. P. Dassanayake, S. K. Maheswaran, and S. Srikumaran
Monomeric Expression of Bovine {beta}2-Integrin Subunits Reveals Their Role in Mannheimia haemolytica Leukotoxin-Induced Biological Effects
Infect. Immun., October 1, 2007; 75(10): 5004 - 5010.
[Abstract] [Full Text] [PDF]


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