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

 Previous Article  |  Next Article 

Infection and Immunity, August 2003, p. 4448-4455, Vol. 71, No. 8
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.8.4448-4455.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Caspase 1 Involvement in Human Monocyte Lysis Induced by Actinobacillus actinomycetemcomitans Leukotoxin

Divisions of Periodontology,¹ Oral Microbiology, Department of Odontology, Faculty of Medicine and Odontology, Umeå University, Umeå, Sweden,² School of Dentistry, Aristotle University of Thessaloniki, Thessaloniki, Greece³

Received 24 February 2003/ Returned for modification 8 May 2003/ Accepted 23 May 2003

Actinobacillus actinomycetemcomitans, an oral bacterium implicated in the etiology of periodontal diseases, produces a leukotoxin that selectively lyses primate neutrophils and monocytes, the major populations of defense cells in the periodontium. Though lysis requires expression of the receptor lymphocyte function-associated molecule 1 (LFA-1) on the cell surface, not all LFA-1-expressing leukocyte populations are equally susceptible to the toxin. In this study, the susceptibility of human leukocytes to leukotoxin-induced lysis is compared to their expression of LFA-1 and the activity of caspase 1. Cytolysis was determined by the activity of lactate dehydrogenase released from peripheral human leukocytes after 1-h exposure to leukotoxin. Monocytes were lysed at leukotoxin concentrations of 5 ng/ml, while the corresponding values for neutrophils and lymphocytes were approximately 10 times greater. Similar LFA-1 expression was found in all susceptible cell populations irrespective of their degree of sensitivity to the toxin. Exposure of monocytes to leukotoxin increased their caspase 1 activity about fivefold within 10 to 20 min. Presence of the caspase 1 inhibitor Ac-YVAD-CMK significantly blocked the leukotoxin-induced lysis of monocytes only. At sublytic concentrations, leukotoxin induced no apoptotic activity in monocytes, as revealed by the lack of caspase 3 activation and DNA fragmentation. Monocytes are the most lysis-sensitive leukocytes for A. actinomycetemcomitans leukotoxin. Their lysis by this toxin depends on caspase 1 activation and proceeds through a process that differs from classical apoptosis.

Editor: J. D. Clements

This article has been cited by other articles:

• 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]  
• Belibasakis, G. N., Johansson, A., Wang, Y., Chen, C., Kalfas, S., Lerner, U. H. (2005). The Cytolethal Distending Toxin Induces Receptor Activator of NF-{kappa}B Ligand Expression in Human Gingival Fibroblasts and Periodontal Ligament Cells. Infect. Immun. 73: 342-351 [Abstract] [Full Text]  
• Kelk, P., Claesson, R., Hanstrom, L., Lerner, U. H., Kalfas, S., Johansson, A. (2005). Abundant Secretion of Bioactive Interleukin-1{beta} by Human Macrophages Induced by Actinobacillus actinomycetemcomitans Leukotoxin. Infect. Immun. 73: 453-458 [Abstract] [Full Text]