Mast cell-derived particles deliver peripheral signals to remote lymph nodes

J Exp Med. 2009 Oct 26;206(11):2455-67. doi: 10.1084/jem.20090805. Epub 2009 Oct 5.

Abstract

During infection, signals from the periphery are known to reach draining lymph nodes (DLNs), but how these molecules, such as inflammatory cytokines, traverse the significant distances involved without dilution or degradation remains unclear. We show that peripheral mast cells, upon activation, release stable submicrometer heparin-based particles containing tumor necrosis factor and other proteins. These complexes enter lymphatic vessels and rapidly traffic to the DLNs. This physiological drug delivery system facilitates communication between peripheral sites of inflammation and remote secondary lymphoid tissues.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Cell-Derived Microparticles / immunology*
  • Cell-Derived Microparticles / metabolism
  • Chitosan / metabolism
  • Cytoplasmic Granules / drug effects
  • Cytoplasmic Granules / metabolism
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Heparin / metabolism
  • Inflammation Mediators / metabolism
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology*
  • Lymph Nodes / pathology
  • Lymphatic Vessels / drug effects
  • Lymphatic Vessels / metabolism
  • Mast Cells / cytology
  • Mast Cells / drug effects
  • Mast Cells / immunology*
  • Mast Cells / ultrastructure
  • Mice
  • Mice, Inbred C57BL
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology*
  • Solubility / drug effects
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Inflammation Mediators
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Heparin
  • Chitosan
  • Tetradecanoylphorbol Acetate