Research ArticlePharmacology

Small Molecule–Mediated Activation of the Integrin CD11b/CD18 Reduces Inflammatory Disease

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Sci. Signal.  06 Sep 2011:
Vol. 4, Issue 189, pp. ra57
DOI: 10.1126/scisignal.2001811

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Stimulated to Stop

The recruitment of leukocytes from the blood to sites of injury in tissues is mediated by interactions between integrins on the surface of leukocytes and ligands on endothelial cells that line the blood vessels. In animals, treatment with integrin antagonists reduces the recruitment of leukocytes from the circulation to tissue sites, but this strategy is not effective in humans. Maiguel et al. took the alternative approach of stimulating integrin activation with small-molecule agonists, which increased the extent of leukocyte adhesion to the endothelium and reduced the number of cells that reached sites of tissue damage in a number of animal models, thus reducing inflammation. Together, these data suggest that stimulating, rather than blocking, integrin activation may be an effective therapy to reduce inflammation.