M Protein, a Classical Bacterial Virulence Determinant, Forms Complexes with Fibrinogen that Induce Vascular Leakage

نویسندگان

  • Heiko Herwald
  • Henning Cramer
  • Matthias Mörgelin
  • Wayne Russell
  • Ulla Sollenberg
  • Anna Norrby-Teglund
  • Hans Flodgaard
  • Lennart Lindbom
  • Lars Björck
چکیده

Increased vascular permeability is a key feature of inflammatory conditions. In severe infections, leakage of plasma from the vasculature induces a life-threatening hypotension. Streptococcus pyogenes, a major human bacterial pathogen, causes a toxic shock syndrome (STSS) characterized by excessive plasma leakage and multi-organ failure. Here we find that M protein, released from the streptococcal surface, forms complexes with fibrinogen, which by binding to beta2 integrins of neutrophils, activate these cells. As a result, neutrophils release heparin binding protein, an inflammatory mediator inducing vascular leakage. In mice, injection of M protein or subcutaneous infection with S. pyogenes causes severe pulmonary damage characterized by leakage of plasma and blood cells. These lesions were prevented by treatment with a beta2 integrin antagonist. In addition, M protein/fibrinogen complexes were identified in tissue biopsies from a patient with necrotizing fasciitis and STSS, further underlining the pathogenic significance of such complexes in severe streptococcal infections.

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عنوان ژورنال:
  • Cell

دوره 116  شماره 

صفحات  -

تاریخ انتشار 2004