Research ArticleSepsis

Targeting Siglecs with a sialic acid–decorated nanoparticle abrogates inflammation

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Science Translational Medicine  02 Sep 2015:
Vol. 7, Issue 303, pp. 303ra140
DOI: 10.1126/scitranslmed.aab3459

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Stopping sepsis

Sepsis is a dreaded diagnosis; clinicians have few tools to fight this generalized inflammatory response to infection that too often results in death. A new nanoparticle described by Spence et al. may prove to be a welcome weapon in the antisepsis arsenal. The nanoparticles are coated with di(α2→8) N-acetylneuraminic acid (NANA), which mimics sialic acid, the natural ligand for a critical anti-inflammatory receptor found on macrophages. This so-called Siglec receptor (sialic acid–binding immunoglobulin-like lectin-E) down-regulates macrophage activation by inflammatory signals released during infection and tissue damage, thereby interrupting the chain of events leading to sepsis. The authors demonstrate that the nanoparticle boosts this anti-inflammatory response in culture, and also show that it improves survival in two mouse models of generalized sepsis and one of pulmonary injury. Most encouraging for the ultimate utility of this nanoparticle in human patients, the nanoparticle is effective in human macrophages and in a sophisticated ex vivo model of human lung edema.