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Infection and Immunity, September 2002, p. 5058-5064, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5058-5068.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Bovine CD18 Is Necessary and Sufficient To Mediate Mannheimia (Pasteurella) haemolytica Leukotoxin-Induced Cytolysis{dagger}

M. S. Deshpande,1 T. C. Ambagala,1 A. P. N. Ambagala,1 M. E. Kehrli, Jr.,2,{ddagger} and S. Srikumaran1*

Department of Veterinary & Biomedical Sciences, University of Nebraska, Lincoln, Nebraska 68583,1 Periparturient Diseases of Cattle Research Unit, National Animal Disease Center, USDA Agricultural Research Service, Ames, Iowa 500102

Received 25 January 2002/ Returned for modification 5 April 2002/ Accepted 8 June 2002

Leukotoxin (Lkt) secreted by Mannheimia (Pasteurella) haemolytica is an RTX toxin which is specific for ruminant leukocytes. Lkt binds to ß2 integrins on the surface of bovine leukocytes. ß2 integrins have a common ß subunit, CD18, that associates with three distinct {alpha} chains, CD11a, CD11b, and CD11c, to give rise to three different ß2 integrins, CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1), and CD11c/CD18 (CR4), respectively. Our earlier studies revealed that Lkt binds to all three ß2 integrins, suggesting that the common ß subunit, CD18, may be the receptor for Lkt. In order to unequivocally elucidate the role of bovine CD18 as a receptor for Lkt, a murine cell line nonsusceptible to Lkt (P815) was transfected with cDNA for bovine CD18. One of the transfectants, 2B2, stably expressed bovine CD18 on the cell surface. The 2B2 transfectant was effectively lysed by Lkt in a concentration-dependent manner, whereas the P815 parent cells were not. Immunoprecipitation of cell surface proteins of 2B2 with monoclonal antibodies specific for bovine CD18 or murine CD11a suggested that bovine CD18 was expressed on the cell surface of 2B2 as a heterodimer with murine CD11a. Expression of bovine CD18 and the Lkt-induced cytotoxicity of 2B2 cells were compared with those of bovine polymorphonuclear neutrophils and lymphocytes. There was a strong correlation between cell surface expression of bovine CD18 and percent cytotoxicity induced by Lkt. These results indicate that bovine CD18 is necessary and sufficient to mediate Lkt-induced cytolysis of target cells.

* Corresponding author. Mailing address: Department of Veterinary & Biomedical Sciences, University of Nebraska—Lincoln, Lincoln, NE 68583-0905. Phone: (402) 472-3319. Fax: (402) 472-9690. E-mail: ssrikumaran1{at}unl.edu.

{dagger} This article is published as ARD Journal Series no. 13606, with the approval of the University of Nebraska Agricultural Research Division.

Editor: A. D. O'Brien

{ddagger} Present address: Pfizer Global Research and Development, Veterinary Medicine Pharmaceutical Discovery, Terre Haute, IN 47808.

Infection and Immunity, September 2002, p. 5058-5064, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5058-5068.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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