Caspase 1 involvement in human monocyte lysis induced by Actinobacillus actinomycetemcomitans leukotoxin.

Abstract

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 > or = 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.

• Authors: P Kelk, A Johansson, R Claesson, L Hänström, S Kalfas
• Journal: Infection and immunity (Infect Immun) Vol. 71 Issue 8 Pg. 4448-55 (Aug 2003) ISSN: 0019-9567 [Print] United States
• PMID: 12874324 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Toxins
• Exotoxins
• Lymphocyte Function-Associated Antigen-1
• leukotoxin
• CASP3 protein, human
• Caspase 3
• Caspases
• Caspase 1

Topics

• Actinobacillus Infections (etiology)
• Aggregatibacter actinomycetemcomitans (pathogenicity)
• Bacterial Toxins (toxicity)
• Caspase 1 (metabolism)
• Caspase 3
• Caspases (metabolism)
• Exotoxins (toxicity)
• HL-60 Cells
• Humans
• In Vitro Techniques
• Lymphocyte Function-Associated Antigen-1 (physiology)
• Lymphocytes (drug effects)
• Monocytes (drug effects, enzymology, immunology)
• Neutrophils (drug effects)
• Periodontitis (etiology)