Microparticles (Ectosomes) Shed by Stored Human Platelets Downregulate Macrophages and Modify the Development of Dendritic Cells

J Immunol. 2011 Jun 1;186(11):6543-52. doi: 10.4049/jimmunol.1002788. Epub 2011 Apr 27.

Abstract

Microparticles (MP) shed by platelets (PLT) during storage have procoagulant activities, but little is known about their properties to modify inflammation or immunity. In this study, we studied the capacity of MP present in PLT concentrates to alter the function of macrophages and dendritic cells (DC). The size of the purified MP was between 100 and 1000 nm, and they expressed phosphatidylserine; surface proteins of PLT (CD61, CD36, CD47), including complement inhibitors (CD55, CD59), but not CD63; and proteins acquired from plasma (C1q, C3 fragments, factor H). These characteristics suggest that the MP shed by PLT are formed by budding from the cell surface, corresponding to ectosomes. The purified PLT ectosomes (PLT-Ect) reduced the release of TNF-α and IL-10 by macrophages activated with LPS or zymosan A. In addition, PLT-Ect induced the immediate release of TGF-β from macrophages, a release that was not modified by LPS or zymosan A. Macrophages had a reduced TNF-α release even 24 h after their exposure to PLT-Ect, suggesting that PLT-Ect induced a modification of the differentiation of macrophages. Similarly, the conventional 6-d differentiation of monocytes to immature DC by IL-4 and GM-CSF was modified by the presence of PLT-Ect during the first 2 d. Immature DC expressed less HLA-DP DQ DR and CD80 and lost part of their phagocytic activity, and their LPS-induced maturation was downmodulated when exposed to PLT-Ect. These data indicate that PLT-Ect shed by stored PLT have intrinsic properties that modify macrophage and DC differentiation toward less reactive states.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-1 Antigen / immunology
  • B7-1 Antigen / metabolism
  • Blood Platelets / immunology*
  • Blood Platelets / metabolism
  • Blood Preservation
  • Blood Proteins / immunology
  • Blood Proteins / metabolism
  • Cell Adhesion
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cell-Derived Microparticles / immunology*
  • Cell-Derived Microparticles / metabolism
  • Cell-Derived Microparticles / ultrastructure
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Down-Regulation
  • Erythrocytes / cytology
  • Erythrocytes / immunology
  • Erythrocytes / metabolism
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • HLA-DP Antigens / immunology
  • HLA-DP Antigens / metabolism
  • Humans
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism
  • Interleukin-4 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Macrophages / cytology
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Microscopy, Electron
  • Monocytes / immunology
  • Monocytes / metabolism
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • B7-1 Antigen
  • Blood Proteins
  • HLA-DP Antigens
  • Lipopolysaccharides
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Granulocyte-Macrophage Colony-Stimulating Factor