Uric Acid Lends a Hand

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Science  28 Nov 2008:
Vol. 322, Issue 5906, pp. 1305
DOI: 10.1126/science.322.5906.1305a

Antigen-presenting cells (APCs) recognize foreign molecules—for instance, the lipopolysaccharides produced by microbial invaders—that bind to cell surface receptors, which mobilize intracellular signal transduction pathways and initiate an anti-microbial response. APCs can also be activated by environmental factors such as the uric acid crystals that are associated with gout. Whether these sorts of particulate materials engage APCs by a similar receptor-based mechanism has been unclear. Using atomic force microscopy (AFM), Ng et al. found that uric acid crystals could bind strongly (100 nN) to cellular membranes via electrostatic interactions. This caused rearrangements of cholesterol-rich lipid rafts within the plasma membrane and stimulated intracellular signaling cascades. These results indicate that, in addition to the classical receptor-ligand pairings, direct cell surface contact by particulate materials can turn on APCs. This approach furthers our understanding of how cells of the immune system can be activated and may reveal the basis of how the adjuvant alum works. — HP*

Immunity 29, 807 (2008).

  • * Helen Pickersgill is a locum editor in Science's editorial department.

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