Receptor-independent, direct membrane binding leads to cell-surface lipid sorting and Syk kinase activation in dendritic cells

Immunity. 2008 Nov 14;29(5):807-18. doi: 10.1016/j.immuni.2008.09.013.


Binding of particulate antigens by antigen-presenting cells is a critical step in immune activation. Previously, we demonstrated that uric acid crystals are potent adjuvants, initiating a robust adaptive immune response. However, the mechanisms of activation are unknown. By using atomic force microscopy as a tool for real-time single-cell activation analysis, we report that uric acid crystals could directly engage cellular membranes, particularly the cholesterol components, with a force substantially stronger than protein-based cellular contacts. Binding of particulate substances activated Syk kinase-dependent signaling in dendritic cells. These observations suggest a mechanism whereby immune cell activation can be triggered by solid structures via membrane lipid alteration without the requirement for specific cell-surface receptors, and a testable hypothesis for crystal-associated arthropathies, inflammation, and adjuvanticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Cell Membrane / immunology
  • Cell Membrane / metabolism*
  • Cholesterol / metabolism*
  • Dendritic Cells / enzymology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Enzyme Activation
  • Gene Knockdown Techniques
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lymphocyte Activation
  • Membrane Lipids / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Atomic Force
  • Myeloid Differentiation Factor 88 / metabolism
  • Protein Binding
  • Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction
  • Syk Kinase
  • Uric Acid / immunology*
  • Uric Acid / metabolism


  • Adaptor Proteins, Vesicular Transport
  • Intracellular Signaling Peptides and Proteins
  • Membrane Lipids
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • TICAM-1 protein, mouse
  • Uric Acid
  • Cholesterol
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • Syk protein, mouse