title: Iron enhances endothelial cell activation in response to Cytomegalovirus or Chlamydia pneumoniae infection.
abstract: BACKGROUND
  Chronic inflammation has been implemented in the pathogenesis of inflammatory diseases like atherosclerosis. Several pathogens like Chlamydia pneumoniae (Cp) and cytomegalovirus (CMV) result in inflammation and thereby are potentially artherogenic. Those infections could trigger endothelial activation, the starting point of the atherogenic inflammatory cascade. Considering the role of iron in a wide range of infection processes, the presence of iron may complicate infection-mediated endothelial activation.
  
  
  METHODS
  Endothelial intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial selectin (E-selectin) expression were measured using flow cytometry, as an indication of endothelial activation. Cytotoxicity was monitored using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Immunostaining was applied to measure Cp and CMV infectivity to endothelial cells.
  
  
  RESULTS
  An increased number of infected endothelial cells in a monolayer population leads to a raised expression of adhesion molecules of the whole cell population, suggesting paracrine interactions. Iron additively up-regulated Cp-induced VCAM-1 expression, whereas synergistically potentiated Cp-induced ICAM-1 expression. Together with CMV, iron also enhanced ICAM-1 and VCAM-1 expression. These iron effects were observed without modulation of the initial infectivity of both microorganisms. Moreover, the effects of iron could be reversed by intracellular iron chelation or radical scavenging, conforming modulating effects of iron on endothelial activation after infections.
  
  
  CONCLUSIONS
  Endothelial response towards chronic infections depends on intracellular iron levels. Iron status in populations positive for Cp or CMV infections should be considered as a potential determinant for the development of atherosclerosis.
authors.affiliation: University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: A E R
authors.initials: AE
authors.lastname: Kartikasari
authors.forename: N A
authors.initials: NA
authors.lastname: Georgiou
authors.forename: M
authors.initials: M
authors.lastname: de Geest
authors.forename: J H
authors.initials: JH
authors.lastname: van Kats-Renaud
authors.forename: J J M
authors.initials: JJ
authors.lastname: Bouwman
authors.forename: B S
authors.initials: BS
authors.lastname: van Asbeck
authors.forename: J J M
authors.initials: JJ
authors.lastname: Marx
authors.forename: F L J
authors.initials: FL
authors.lastname: Visseren
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism; D002690:Chlamydia Infections / Q000378:metabolism; D016993:Chlamydophila pneumoniae; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections; D019040:E-Selectin / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007501:Iron