This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jeyaseelan, S.
Right arrow Articles by Maheswaran, S. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jeyaseelan, S.
Right arrow Articles by Maheswaran, S. K.

 Previous Article  |  Next Article 

Infection and Immunity, January 2000, p. 72-79, Vol. 68, No. 1
0019-9567/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Lymphocyte Function-Associated Antigen 1 Is a Receptor for Pasteurella haemolytica Leukotoxin in Bovine Leukocytes

S. Jeyaseelan,1 S. L. Hsuan,1 M. S. Kannan,1 B. Walcheck,1 J. F. Wang,2 M. E. Kehrli,3 E. T. Lally,2 G. C. Sieck,4 and S. K. Maheswaran1,*

Department of Veterinary PathoBiology, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota 551081; Leon Levy Research Center for Oral Biology, University of Pennsylvania, Philadelphia, Pennsylvania 191042; Metabolic Diseases and Immunology Research Unit, National Animal Disease Center, Ames, Iowa 500103; and Departments of Anesthesiology and of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota 559054

Received 13 August 1999/Returned for modification 4 October 1999/Accepted 14 October 1999

Pasteurella (Mannheimia) haemolytica leukotoxin (Lkt) causes cell type- and species-specific effects in ruminant leukocytes. Recent studies indicate that P. haemolytica Lkt binds to bovine CD18, the common subunit of all beta 2 integrins. We designed experiments with the following objectives: to identify which member of the beta 2 integrins is a receptor for Lkt; to determine whether Lkt binding to the receptor is target cell (bovine leukocytes) specific; to define the relationships between Lkt binding to the receptor, calcium elevation, and cytolysis; and to determine whether a correlation exists between Lkt receptor expression and the magnitude of target cell cytolysis. We compared Lkt-induced cytolysis in neutrophils from control calves and from calves with bovine leukocyte adhesion deficiency (BLAD), because neutrophils from BLAD-homozygous calves exhibit reduced beta 2 integrin expression. The results demonstrate for the first time that Lkt binds to bovine CD11a and CD18 (lymphocyte function-associated antigen 1 [LFA-1]). The binding was abolished by anti-CD11a or anti-CD18 monoclonal antibody (MAb). Lkt-induced calcium elevation in bovine alveolar macrophages (BAMs) was inhibited by anti-CD11a or anti-CD18 MAb (65 to 94% and 37 to 98%, respectively, at 5 and 50 Lkt units per ml; P < 0.05). Lkt-induced cytolysis in neutrophils and BAMs was also inhibited by anti-CD11a or anti-CD18 MAb in a concentration-dependent manner. Lkt bound to porcine LFA-1 but did not induce calcium elevation or cytolysis. In neutrophils from BLAD calves, Lkt-induced cytolysis was decreased by 44% compared to that of neutrophils from control calves (P < 0.05). These results indicate that LFA-1 is a Lkt receptor, Lkt binding to LFA-1 is not target cell specific, Lkt binding to bovine LFA-1 correlates with calcium elevation and cytolysis, and bovine LFA-1 expression correlates with the magnitude of Lkt-induced target cell cytolysis.

* Corresponding author. Mailing address: Department of Veterinary PathoBiology, University of Minnesota, 1971 Commonwealth Ave., St. Paul, MN 55108. Phone: (612) 625-6264. Fax: (612) 624-4785. E-mail: mahes001{at}maroon.tc.umn.edu.

Infection and Immunity, January 2000, p. 72-79, Vol. 68, No. 1
0019-9567/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Shanthalingam, S., Srikumaran, S. (2009). Intact signal peptide of CD18, the {beta}-subunit of {beta}2-integrins, renders ruminants susceptible to Mannheimia haemolytica leukotoxin. Proc. Natl. Acad. Sci. USA 106: 15448-15453 [Abstract] [Full Text]  
  • Atapattu, D. N., Albrecht, R. M., McClenahan, D. J., Czuprynski, C. J. (2008). Dynamin-2-Dependent Targeting of Mannheimia haemolytica Leukotoxin to Mitochondrial Cyclophilin D in Bovine Lymphoblastoid Cells. Infect. Immun. 76: 5357-5365 [Abstract] [Full Text]  
  • Dassanayake, R. P., Liu, W., Davis, W. C., Foreyt, W. J., Srikumaran, S. (2008). Bighorn Sheep {beta}2-Integrin LFA-1 Serves as a Receptor for Mannheimia haemolytica Leukotoxin. J Wildl Dis 44: 743-747 [Abstract] [Full Text]  
  • Morova, J., Osicka, R., Masin, J., Sebo, P. (2008). RTX cytotoxins recognize {beta}2 integrin receptors through N-linked oligosaccharides. Proc. Natl. Acad. Sci. USA 105: 5355-5360 [Abstract] [Full Text]  
  • McClenahan, D., Hellenbrand, K., Atapattu, D., Aulik, N., Carlton, D., Kapur, A., Czuprynski, C. (2008). Effects of Lipopolysaccharide and Mannheimia haemolytica Leukotoxin on Bovine Lung Microvascular Endothelial Cells and Alveolar Epithelial Cells. CVI 15: 338-347 [Abstract] [Full Text]  
  • Dileepan, T., Kachlany, S. C., Balashova, N. V., Patel, J., Maheswaran, S. K. (2007). Human CD18 Is the Functional Receptor for Aggregatibacter actinomycetemcomitans Leukotoxin. Infect. Immun. 75: 4851-4856 [Abstract] [Full Text]  
  • Atapattu, D. N., Czuprynski, C. J. (2007). Mannheimia haemolytica Leukotoxin Binds to Lipid Rafts in Bovine Lymphoblastoid Cells and Is Internalized in a Dynamin-2- and Clathrin-Dependent Manner. Infect. Immun. 75: 4719-4727 [Abstract] [Full Text]  
  • Dassanayake, R. P., Maheswaran, S. K., Srikumaran, S. (2007). Monomeric Expression of Bovine {beta}2-Integrin Subunits Reveals Their Role in Mannheimia haemolytica Leukotoxin-Induced Biological Effects. Infect. Immun. 75: 5004-5010 [Abstract] [Full Text]  
  • Atapattu, D. N., Czuprynski, C. J. (2005). Mannheimia haemolytica Leukotoxin Induces Apoptosis of Bovine Lymphoblastoid Cells (BL-3) via a Caspase-9-Dependent Mitochondrial Pathway. Infect. Immun. 73: 5504-5513 [Abstract] [Full Text]  
  • Gopinath, R. S., Ambagala, T. C., Deshpande, M. S., Donis, R. O., Srikumaran, S. (2005). Mannheimia (Pasteurella) haemolytica Leukotoxin Binding Domain Lies within Amino Acids 1 to 291 of Bovine CD18. Infect. Immun. 73: 6179-6182 [Abstract] [Full Text]  
  • Dileepan, T., Kannan, M. S., Walcheck, B., Thumbikat, P., Maheswaran, S. K. (2005). Mapping of the Binding Site for Mannheimia haemolytica Leukotoxin within Bovine CD18. Infect. Immun. 73: 5233-5237 [Abstract] [Full Text]  
  • Starr, A. E., Dan, T., Minhas, K., Shewen, P. E., Coomber, B. L. (2004). Potential Involvement of Gelatinases and Their Inhibitors in Mannheimia haemolytica Pneumonia in Cattle. Infect. Immun. 72: 4393-4400 [Abstract] [Full Text]  
  • Martin, C., Requero, M.-A., Masin, J., Konopasek, I., Goni, F. M., Sebo, P., Ostolaza, H. (2004). Membrane Restructuring by Bordetella pertussis Adenylate Cyclase Toxin, a Member of the RTX Toxin Family. J. Bacteriol. 186: 3760-3765 [Abstract] [Full Text]  
  • Deshpande, M. S., Ambagala, T. C., Ambagala, A. P. N., Kehrli, M. E. Jr., Srikumaran, S. (2002). Bovine CD18 Is Necessary and Sufficient To Mediate Mannheimia (Pasteurella) haemolytica Leukotoxin-Induced Cytolysis. Infect. Immun. 70: 5058-5064 [Abstract] [Full Text]  
  • Leite, F., O'Brien, S., Sylte, M. J., Page, T., Atapattu, D., Czuprynski, C. J. (2002). Inflammatory Cytokines Enhance the Interaction of Mannheimia haemolytica Leukotoxin with Bovine Peripheral Blood Neutrophils In Vitro. Infect. Immun. 70: 4336-4343 [Abstract] [Full Text]  
  • Davies, R. L., Campbell, S., Whittam, T. S. (2002). Mosaic Structure and Molecular Evolution of the Leukotoxin Operon (lktCABD) in Mannheimia (Pasteurella) haemolytica, Mannheimia glucosida, and Pasteurella trehalosi. J. Bacteriol. 184: 266-277 [Abstract] [Full Text]  
  • Jeyaseelan, S., Kannan, M. S., Briggs, R. E., Thumbikat, P., Maheswaran, S. K. (2001). Mannheimia haemolytica Leukotoxin Activates a Nonreceptor Tyrosine Kinase Signaling Cascade in Bovine Leukocytes, Which Induces Biological Effects. Infect. Immun. 69: 6131-6139 [Abstract] [Full Text]  
  • Davies, R. L., Whittam, T. S., Selander, R. K. (2001). Sequence Diversity and Molecular Evolution of the Leukotoxin (lktA) Gene in Bovine and Ovine Strains of Mannheimia (Pasteurella) haemolytica. J. Bacteriol. 183: 1394-1404 [Abstract] [Full Text]  
  • Leite, F., Brown, J. F., Sylte, M. J., Briggs, R. E., Czuprynski, C. J. (2000). Recombinant Bovine Interleukin-1beta Amplifies the Effects of Partially Purified Pasteurella haemolytica Leukotoxin on Bovine Neutrophils in a beta 2-Integrin-Dependent Manner. Infect. Immun. 68: 5581-5586 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»