Shock Therapy

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Science  20 Feb 2004:
Vol. 303, Issue 5661, pp. 1107
DOI: 10.1126/science.303.5661.1107b

Streptococcus pyogenes is a versatile bacterial pathogen that causes a wide range of illnesses in humans, from mild throat infections to toxic shock syndrome (STSS). STSS is an acute infection characterized by vascular injury and multi-organ failure. Even with aggressive treatment, STSS is fatal in 30 to 70% of cases, so new therapies are desperately needed.

A mouse model of S. pyogenes infection has helped researchers delineate the pathophysiological chain of events leading to STSS. Herwald et al. find that a complex consisting of a protein shed by the bacteria (M1) and a blood clotting factor (fibrinogen) binds to and activates polymorphonuclear neutrophils (PMNs) of the immune system through interaction with β2-integrins. Rather than ingesting and destroying the bacteria, as they are designed to do, the activated PMNs undergo a process called “frustrated phagocytosis.” As a result, they release proteins that induce vascular leakage and massive inflammation, which in turn causes severe tissue damage. Importantly, lung damage in this mouse model was diminished by administration of a peptide that disrupts the interaction between fibrinogen and β2-integrins. — PAK

Cell 116, 367 (2004).

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