title: Microparticles from human atherosclerotic plaques promote endothelial ICAM-1-dependent monocyte adhesion and transendothelial migration.
abstract: OBJECTIVE
  Membrane-shed submicron microparticles (MPs) released following cell activation or apoptosis accumulate in atherosclerotic plaques, where they stimulate endothelial proliferation and neovessel formation. The aim of the study was to assess whether or not MPs isolated from human atherosclerotic plaques contribute to increased endothelial adhesion molecules expression and monocyte recruitment.
  
  
  RESULTS
  Human umbilical vein and coronary artery endothelial cells were exposed to MPs isolated from endarterectomy specimens (n=62) and characterized by externalized phosphatidylserine. Endothelial exposure to plaque, but not circulating, MPs increased ICAM-1 levels in a concentration-dependant manner (3.4-fold increase) without affecting ICAM-1 mRNA levels. Plaque MPs harbored ICAM-1 and transferred this adhesion molecule to endothelial cell membrane in a phosphatidylserine-dependent manner. MP-borne ICAM-1 was functionally integrated into cell membrane as demonstrated by the increased ERK1/2 phosphorylation following ICAM-1 ligation. Plaque MPs stimulated endothelial monocyte adhesion both in culture and in isolated perfused mouse carotid. This effect was also observed under flow condition and was prevented by anti-LFA-1 and anti-ICAM-1 neutralizing antibodies. MPs isolated from symptomatic plaques were more potent in stimulating monocyte adhesion than MPs from asymptomatic patients. Plaque MPs did not affect the release of interleukin-6, interleukin-8, or MCP-1, nor the expression of VCAM-1 and E-selectin.
  
  
  CONCLUSIONS
  These results demonstrate that MPs isolated from human atherosclerotic plaques transfer ICAM-1 to endothelial cells to recruit inflammatory cells and suggest that plaque MPs promote atherosclerotic plaque progression.
authors.affiliation: Paris Centre de recherche Cardiovasculaire à l'HEGP, INSERM U970, 56, rue Leblanc, 75737 Paris cedex 15, France. chantal.boulanger@inserm.fr.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Rautou
authors.forename: Aurélie S
authors.initials: AS
authors.lastname: Leroyer
authors.forename: Bhama
authors.initials: B
authors.lastname: Ramkhelawon
authors.forename: Cécile
authors.initials: C
authors.lastname: Devue
authors.forename: Dominique
authors.initials: D
authors.lastname: Duflaut
authors.forename: Anne-Clémence
authors.initials: AC
authors.lastname: Vion
authors.forename: Gilles
authors.initials: G
authors.lastname: Nalbone
authors.forename: Yves
authors.initials: Y
authors.lastname: Castier
authors.forename: Guy
authors.initials: G
authors.lastname: Leseche
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lehoux
authors.forename: Alain
authors.initials: A
authors.lastname: Tedgui
authors.forename: Chantal M
authors.initials: CM
authors.lastname: Boulanger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D055252:Cell-Derived Microparticles / Q000473:pathology*; D002478:Cells, Cultured; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology* / Q000502:physiology; D058226:Plaque, Atherosclerotic / Q000473:pathology* / Q000503:physiopathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D019040:E-Selectin; D015850:Interleukin-6; D016209:Interleukin-8; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1