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Infection and Immunity, August 2002, p. 4609-4620, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4609-4620.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Fusobacterium necrophorum Leukotoxin Induces Activation and Apoptosis of Bovine Leukocytes

Sanjeevkumar Narayanan, George C. Stewart, M. M. Chengappa, Lloyd Willard, Wilma Shuman, Melinda Wilkerson, and T. G. Nagaraja^*

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas 66506

Received 2 November 2001/ Returned for modification 21 December 2001/ Accepted 23 April 2002

Fusobacterium necrophorum, a gram-negative, rod-shaped, anaerobic bacterium, is a primary or secondary etiological agent in a variety of necrotic, purulent infections in humans and animals. Its major virulence factor is leukotoxin, a high-molecular-weight secreted protein, primarily toxic to ruminant leukocytes. In this study, bovine peripheral blood leukocytes were exposed to various concentrations of immunoaffinity-purified leukotoxin and the cytotoxicity was analyzed by flow cytometry and scanning and transmission electron microscopy. At very low toxin concentrations, polymorphonuclear leukocytes (PMNs) showed activation, as indicated by translocation of primary and secondary granules to the periphery of the cytoplasm. Furthermore, these cells showed changes characteristic of apoptosis, including decreased cell size, organelle condensation, cytoplasmic membrane blebbing (zeiosis), and chromatin condensation and margination, and decrease in cellular DNA content. At moderately high concentrations of leukotoxin, bovine mononuclear cells were also induced to undergo programmed cell death. At very high concentrations, leukotoxin caused necrotic cell death of bovine peripheral leukocytes. The ability of F. necrophorum leukotoxin to modulate the host immune system by its toxicity, including cellular activation of PMNs and apoptosis-mediated killing of phagocytes and immune effector cells, represents a potentially important mechanism of its pathogenesis.

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* Corresponding author. Mailing address: Department of Diagnostic Medicine/Pathobiology, 305 Coles Hall, Manhattan, KS 66506-5606. Phone: (785) 532-1214. Fax: (785) 532-4851. E-mail: Tnagaraj{at}vet.ksu.edu.

This paper is contribution no. 02-17-j from the Kansas Agricultural Experiment Station.

Editor: J. T. Barbieri

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Infection and Immunity, August 2002, p. 4609-4620, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4609-4620.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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