Effects of Aggregatibacter actinomycetemcomitans leukotoxin on endothelial cells

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