title: 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.affiliation: Division of Periodontology, Department of Odontology, Faculty of Medicine and Odontology, Umeå University, Umeå, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Kelk
authors.forename: A
authors.initials: A
authors.lastname: Johansson
authors.forename: R
authors.initials: R
authors.lastname: Claesson
authors.forename: L
authors.initials: L
authors.lastname: Hänström
authors.forename: S
authors.initials: S
authors.lastname: Kalfas
mesh_terms: D000189:Actinobacillus Infections / Q000209:etiology; D016976:Aggregatibacter actinomycetemcomitans / Q000472:pathogenicity*; D001427:Bacterial Toxins / Q000633:toxicity*; D020170:Caspase 1 / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D005098:Exotoxins / Q000633:toxicity*; D018922:HL-60 Cells; D006801:Humans; D066298:In Vitro Techniques; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology* / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects; D010518:Periodontitis / Q000209:etiology
chemical_list: D001427:Bacterial Toxins; D005098:Exotoxins; D016169:Lymphocyte Function-Associated Antigen-1; C018579:leukotoxin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1