Effects of Aggregatibacter actinomycetemcomitans leukotoxin on endothelial cells

Dietmann, A; Millonig, A; Combes, V; Couraud, PO; Kachlany, SC; Grau, GE

Effects of Aggregatibacter actinomycetemcomitans leukotoxin on endothelial cells

Dietmann, A Millonig, A Combes, V

Couraud, PO Kachlany, SC Grau, GE

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Publication Type:: Journal Article
Citation:: Microbial Pathogenesis, 2013, 61-62 pp. 43 - 50
Issue Date:: 2013-08-01

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Field	Value	Language
dc.contributor.author	Dietmann, A	en_US
dc.contributor.author	Millonig, A	en_US
dc.contributor.author	Combes, V https://orcid.org/0000-0003-2178-3596	en_US
dc.contributor.author	Couraud, PO	en_US
dc.contributor.author	Kachlany, SC	en_US
dc.contributor.author	Grau, GE	en_US
dc.date.available	2013-05-01	en_US
dc.date.issued	2013-08-01	en_US
dc.identifier.citation	Microbial Pathogenesis, 2013, 61-62 pp. 43 - 50	en_US
dc.identifier.issn	0882-4010	en_US
dc.identifier.uri	http://hdl.handle.net/10453/116222
dc.description.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 (500ng/ml to 5μg/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 72h. Between 500ng/ml and 5μg/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. •LtxA has anti-proliferative effects on endothelial cells.•LtxA induces a G2/M phase cell cycle arrest in endothelial cells.•LtxA induces apoptosis in endothelial cells.•LtxA increased expression of ICAM-1 and VCAM-1 in endothelial cells. © 2013 The Authors.	en_US
dc.relation.ispartof	Microbial Pathogenesis	en_US
dc.relation.isbasedon	10.1016/j.micpath.2013.05.001	en_US
dc.subject.classification	Microbiology	en_US
dc.subject.mesh	Endothelial Cells	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Intercellular Adhesion Molecule-1	en_US
dc.subject.mesh	Vascular Cell Adhesion Molecule-1	en_US
dc.subject.mesh	Bacterial Toxins	en_US
dc.subject.mesh	Exotoxins	en_US
dc.subject.mesh	Virulence Factors	en_US
dc.subject.mesh	Apoptosis	en_US
dc.subject.mesh	Cell Proliferation	en_US
dc.subject.mesh	M Phase Cell Cycle Checkpoints	en_US
dc.subject.mesh	G2 Phase Cell Cycle Checkpoints	en_US
dc.subject.mesh	Aggregatibacter actinomycetemcomitans	en_US
dc.title	Effects of Aggregatibacter actinomycetemcomitans leukotoxin on endothelial cells	en_US
dc.type	Journal Article
utslib.citation.volume	61-62	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	1107 Immunology	en_US
utslib.for	1108 Medical Microbiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.publication-status	Published	en_US
pubs.volume	61-62	en_US

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 (500ng/ml to 5μg/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 72h. Between 500ng/ml and 5μg/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. •LtxA has anti-proliferative effects on endothelial cells.•LtxA induces a G2/M phase cell cycle arrest in endothelial cells.•LtxA induces apoptosis in endothelial cells.•LtxA increased expression of ICAM-1 and VCAM-1 in endothelial cells. © 2013 The Authors.

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http://hdl.handle.net/10453/116222