title: Mast cell-derived exosomes activate endothelial cells to secrete plasminogen activator inhibitor type 1.
abstract: OBJECTIVE
  Previous studies supported the contribution of exosomes to an acellular mode of communication, leading to intercellular transfer of molecules. In this study we provide evidence that mast cell-derived exosomes induce plasminogen activator inhibitor type 1 (PAI-1) expression in endothelial cells, detectable at the level of PAI-1 mRNA and protein synthesis. The stimulating effect was also measured at the level of PAI-1 promoter activity.
  
  
  RESULTS
  To identify components responsible for this activity, exosome proteins were separated by 2-dimensional PAGE, and protein spots were identified by microsequencing using electrospray (ISI-Q-TOF-Micromass) spectrometer. Components of 3 independent systems that can be involved in activation of endothelial cells, namely the prothrombinase complex, tumor necrosis factor-alpha, and angiotensinogen precursors were identified. Procoagulant activity of exosomes was confirmed by a thrombin generation assay using a specific chromogenic substrate. Because the potential of mast cell-derived exosomes to induce PAI-1 expression was completely abolished by hirudin, thrombin generated on exosomes seems to be responsible for this activity.
  
  
  CONCLUSIONS
  It can be concluded that mast cell-derived exosomes via significant upregulation of PAI-1 secretion from endothelial cells may provide feedback between the characteristically increased PAI-1 levels and procoagulant states, both observed in diverse syndromes manifesting as endothelial cell dysfunction.
authors.affiliation: Center of Medical Biology, Polish Academy of Sciences, Poland.
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Nedawi
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.forename: Czeslaw S
authors.initials: CS
authors.lastname: Cierniewski
mesh_terms: D002450:Cell Communication / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D025461:Feedback, Physiological / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D012333:RNA, Messenger / Q000032:analysis; D013917:Thrombin / Q000378:metabolism; D020298:U937 Cells; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D013917:Thrombin