title: Effects of Aggregatibacter actinomycetemcomitans leukotoxin on endothelial cells.
abstract: Aggregatibacter actinomycetemcomitans is a human pathogen that produces leukotoxin (LtxA) as a major virulence factor. In this study the effect of LtxA on microvascular endothelial cell viability and phenotype was studied. High doses of single LtxA treatment (500 ng/ml to 5 μg/ml) significantly and irreversibly decreased cell proliferation and induced apoptosis, as assessed by tetrazolium salt and annexin V assay, respectively. Apoptosis was partially inhibited by the pan-caspase inhibitor, z-VAD-fmk. LtxA caused a cell cycle arrest in the G2/M phase after 72 h. Between 500 ng/ml and 5 μg/ml, after long- or short-term stimulation LtxA increased the expression of ICAM-1 and VCAM-1, as well as the percentages of endothelial cells expressing these adhesion molecules. Thus, A. actinomycetemcomitans LtxA has substantial pro-inflammatory effects on human brain endothelial cells by upregulation of ICAM-1 and VCAM-1. Furthermore, LtxA in higher concentration was found to decrease proliferation and induces apoptosis in microvascular endothelial cells.
authors.affiliation: Department of Pathology, Vascular Immunology Unit, Sydney Medical School, The University of Sydney, 92-94 Parramatta Rd, Camperdown, 2050 NSW, Australia. Anelia.Dietmann@i-med.ac.at
authors.forename: Anelia
authors.initials: A
authors.lastname: Dietmann
authors.forename: Alban
authors.initials: A
authors.lastname: Millonig
authors.forename: Valery
authors.initials: V
authors.lastname: Combes
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Couraud
authors.forename: Scott C
authors.initials: SC
authors.lastname: Kachlany
authors.forename: Georges E
authors.initials: GE
authors.lastname: Grau
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000378:metabolism* / Q000472:pathogenicity*; D017209:Apoptosis / Q000187:drug effects; D001427:Bacterial Toxins / Q000378:metabolism / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005098:Exotoxins / Q000378:metabolism / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D037521:Virulence Factors / Q000378:metabolism / Q000494:pharmacology
chemical_list: D001427:Bacterial Toxins; D005098:Exotoxins; D019010:Vascular Cell Adhesion Molecule-1; D037521:Virulence Factors; C018579:leukotoxin; D018799:Intercellular Adhesion Molecule-1
keywords: Activation; Aggregatibacter actinomycetemcomitans; Apoptosis; Endothelium; Leukotoxin