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Receptor-Independent, Direct Membrane Binding Leads to Cell-Surface Lipid Sorting and Syk Kinase Activation in Dendritic Cells

2008; Cell Press; Volume: 29; Issue: 5 Linguagem: Inglês

10.1016/j.immuni.2008.09.013

1097-4180

Gilbert Ng, Karan Sharma, Sandra Ward, Melanie D. Desrosiers, Leslie Stephens, W. Michael Schoel, Tonglei Li, Clifford A. Lowell, Chang‐Chun Ling, Matthias Amrein, Yan Shi,

Immune Cell Function and Interaction

Summary 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.