Effects of Aggregatibacter actinomycetemcomitans leukotoxin on endothelial cells

Microb Pathog. Aug-Sep 2013;61-62:43-50. doi: 10.1016/j.micpath.2013.05.001. Epub 2013 May 9.

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.

Keywords: Activation; Aggregatibacter actinomycetemcomitans; Apoptosis; Endothelium; Leukotoxin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggregatibacter actinomycetemcomitans / metabolism*
  • Aggregatibacter actinomycetemcomitans / pathogenicity*
  • Apoptosis / drug effects
  • Bacterial Toxins / metabolism
  • Bacterial Toxins / pharmacology
  • Cell Proliferation / drug effects
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Exotoxins / metabolism
  • Exotoxins / pharmacology*
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Intercellular Adhesion Molecule-1 / drug effects
  • Intercellular Adhesion Molecule-1 / metabolism
  • M Phase Cell Cycle Checkpoints / drug effects
  • Vascular Cell Adhesion Molecule-1 / drug effects
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Virulence Factors / metabolism
  • Virulence Factors / pharmacology

Substances

  • Bacterial Toxins
  • Exotoxins
  • Vascular Cell Adhesion Molecule-1
  • Virulence Factors
  • leukotoxin
  • Intercellular Adhesion Molecule-1