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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.
AuthorsP Kelk, A Johansson, R Claesson, L Hänström, S Kalfas
JournalInfection and immunity (Infect Immun) Vol. 71 Issue 8 Pg. 4448-55 (Aug 2003) ISSN: 0019-9567 [Print] United States
PMID12874324 (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)

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