title: Outer membrane vesicles alter inflammation and coagulation mediators.
abstract: BACKGROUND
  Outer membrane vesicles (OMVs) were previously shown to be capable of initiating the inflammatory response seen in the transition of an infection to sepsis. However, another tenet of sepsis is the development of a hypercoagulable state and the role of OMVs in the development of this hypercoagulability has not been evaluated. The objective of this study was to evaluate the ability of OMVs to elicit endothelial mediators of coagulation and inflammation and induce platelet activation.
  
  
  METHODS
  Human umbilical vein endothelial cells (HUVECs) were incubated with OMVs and were analyzed for the expression of tissue factor (TF), thrombomodulin, and the adhesion molecules P-selectin and E-selectin. Supernatants of OMV-treated HUVECs were mixed with whole blood and assessed for prothrombotic monocyte-platelet aggregates (MPA).
  
  
  RESULTS
  OMVs induce significantly increased expression of TF, E-selectin, and P-selectin, whereas, the expression of thrombomodulin by HUVECs is significantly decreased (P < 0.05). The lipopolysaccharide inhibitor clearly inhibited the expression of E-selectin following incubation with OMVs, although its impact on TF and thrombomodulin expression was nominal. Incubation of whole blood with supernatant from HUVECs exposed to OVMs resulted in increased MPAs.
  
  
  CONCLUSIONS
  This study demonstrates that, at the cellular level, OMVs from pathogenic bacteria play a complex role in endothelial activation. Although OMV-bound lipopolysaccharide modulates inflammatory proteins, including E-selectin, it has a negligible effect on the tested coagulation mediators. Additionally, endothelial activation by OMVs facilitates platelet activation as indicated by increased MPAs. By influencing the inflammatory and coagulation cascades, OMVs may contribute to the hypercoagulable response seen in sepsis.
authors.affiliation: Department of Surgery, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Soult
authors.affiliation: Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Dobrydneva
authors.affiliation: Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Kamal H
authors.initials: KH
authors.lastname: Wahab
authors.affiliation: Department of Surgery, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: L D
authors.initials: LD
authors.lastname: Britt
authors.affiliation: Department of Surgery, Eastern Virginia Medical School, Norfolk, Virginia. Electronic address: sullivcj@evms.edu.
authors.forename: Claretta J
authors.initials: CJ
authors.lastname: Sullivan
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000276:immunology* / Q000494:pharmacology; D001777:Blood Coagulation / Q000276:immunology*; D055252:Cell-Derived Microparticles / Q000276:immunology*; D022162:Cytoplasmic Vesicles / Q000276:immunology* / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000276:immunology; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism; D018180:Thrombomodulin / Q000378:metabolism; D019851:Thrombophilia / Q000276:immunology* / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D019040:E-Selectin; D008070:Lipopolysaccharides; D019007:P-Selectin; C546936:SELE protein, human; C546931:THBD protein, human; D018180:Thrombomodulin; D013925:Thromboplastin
keywords: Coagulation; Endothelium; Monocyte–platelet aggregation; Outer membrane vesicles; Sepsis; Thrombomodulin; Tissue factor