title: Periodontopathogens induce soluble P-selectin release by endothelial cells and platelets.
abstract: BACKGROUND
  Soluble P-selectin plays a pivotal role in inflammation and the development of thrombotic and cardiovascular disease. Accordingly, elevated levels of soluble P-selectin are found in periodontitis and (other forms of) inflammatory diseases. However, the cellular source of soluble P-selectin in periodontitis and the effects of periodontopathogens on P-selectin release are unknown.
  
  
  METHODS
  Soluble P-selectin was determined in 26 patients with periodontitis and 19 controls. Furthermore, human endothelial cells and platelets were investigated for their ability to elicit soluble and surface P-selectin in response to periodontopathogens A. actinomycetemcomitans Y4 and P. gingivalis. Moreover surface E-selectin and ICAM-1 expression as well as NFκB translocation in response to these bacteria were determined on endothelial cells as well as the formation of platelet-leukocyte complexes.
  
  
  RESULTS
  Plasma levels of soluble P-selectin are significantly elevated in periodontitis and correlate with severity of disease and bacterial infection. Stimulation of endothelial cells with periodontopathogens results in rapid surface expression of P-selectin but does not induce NFκB translocation and subsequent de novo synthesis of P-selectin, E-selectin or ICAM-1. In platelets, bacterial stimulation leads to surface expression of P-selectin and fosters the formation of platelet-leukocyte aggregates within minutes. P-selectin is rapidly shed from the surface of platelets and endothelial cells and results in increased levels of soluble P-selectin.
  
  
  CONCLUSIONS
  Periodontopathogens are able to directly cause activation of endothelial cells and platelets within minutes. Given that transient periodontitis-associated bacteremia commonly occurs after tooth brushing or chewing, our data suggest that reduction of periodontopathogens might result in potential cardiovascular benefits.
authors.affiliation: Institute of Physiology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria. alice.assinger@meduniwien.ac.at
authors.forename: Alice
authors.initials: A
authors.lastname: Assinger
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Buchberger
authors.forename: Markus
authors.initials: M
authors.lastname: Laky
authors.forename: Azadeh
authors.initials: A
authors.lastname: Esfandeyari
authors.forename: Christine
authors.initials: C
authors.lastname: Brostjan
authors.forename: Ivo
authors.initials: I
authors.lastname: Volf
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000472:pathogenicity*; D001792:Blood Platelets / Q000276:immunology* / Q000382:microbiology; D016022:Case-Control Studies; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology* / Q000382:microbiology; D005089:Exocytosis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D019007:P-Selectin / Q000097:blood / Q000378:metabolism*; D010518:Periodontitis / Q000276:immunology* / Q000382:microbiology; D010973:Platelet Adhesiveness; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D021381:Protein Transport; D013997:Time Factors; D015854:Up-Regulation; D020302:Weibel-Palade Bodies / Q000276:immunology / Q000382:microbiology
chemical_list: D016328:NF-kappa B; D019007:P-Selectin; C546937:SELP protein, human; D018799:Intercellular Adhesion Molecule-1