Free access
Vet. Res.
Volume 36, Number 5-6, September-December 2005
Page(s) 771 - 786
How to cite this article Vet. Res. (2005) 771-786
Vet. Res. 36 (2005) 771-786
DOI: 10.1051/vetres:2005036

Characterization of Mannheimia (Pasteurella) haemolytica leukotoxin interaction with bovine alveolar macrophage $\beta$2 integrins

Praveen Thumbikat, Thamotharampillai Dileepan, Mathur S. Kannan and Samuel K. Maheswaran

Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota 55108, USA

(Received 1 November 2004; accepted 21 March 2005)

Abstract - Mannheimia (Pasteurella) haemolytica, the etiologic agent of bovine pneumonic mannheimiosis, produces an exotoxic leukotoxin. The leukotoxin (LktA) is a member of the RTX (repeats in toxin) family of bacterial cytolysins and is distinguished from other toxins by its unique target cell specificity to ruminant leukocytes occurring through binding to a specific receptor. We have demonstrated previously that the $\beta$2 integrin LFA-1 is a receptor for LktA in bovine leukocytes and is involved in leukotoxin-induced biological effects. However the subunits within LFA-1 involved in binding to LktA, and post-binding signaling leading to cellular activation have not been well characterized. The purpose of our study was to pinpoint these precise subunits on bovine alveolar macrophages and to characterize their interaction with LktA. The results in this study indicate that although LktA can efficiently bind to the CD18 subunit of both LFA-1 and Mac-1, post-binding signaling events including elevation of intracellular calcium and CD18 tail phosphorylation are only observed through LFA-1. Furthermore, LktA also binds to the CD11a subunit of LFA-1. LktA binding to CD11a could be inhibited by a small molecule inhibitor of the I(inserted)-domain, the major ligand binding interface on CD11a. I-domain inhibition significantly blunts LktA-induced intracellular calcium elevation and tyrosine phosphorylation of the CD18 tail. Based on our results we suggest that LFA-1 serves as the functional leukotoxin receptor on bovine alveolar macrophages.

Key words: Mannheimia haemolytica leukotoxin / receptor / lymphocyte function associated antigen-1 / signaling

Corresponding author: Samuel K. Maheswaran

© INRA, EDP Sciences 2005

What is OpenURL?

The OpenURL standard is a protocol for transmission of metadata describing the resource that you wish to access.

An OpenURL link contains article metadata and directs it to the OpenURL server of your choice. The OpenURL server can provide access to the resource and also offer complementary services (specific search engine, export of references...). The OpenURL link can be generated by different means.

  • If your librarian has set up your subscription with an OpenURL resolver, OpenURL links appear automatically on the abstract pages.
  • You can define your own OpenURL resolver with your EDPS Account.
    In this case your choice will be given priority over that of your library.
  • You can use an add-on for your browser (Firefox or I.E.) to display OpenURL links on a page (see You should disable this module if you wish to use the OpenURL server that you or your library have defined.