M protein, a Classical Bacteria Virulence Determinant, Forms Complexes with Fibrinogen that Induce Vascular Leakage
M protein, a Classical Bacteria Virulence Determinant, Forms Complexes with Fibrinogen that Induce Vascular Leakage
(Herwald, H. et al., 2004, Cell, 116: 367-379)
Speaker: 陳毓雯
Commentator: 劉清泉 醫師
Time: 15:00~16:00 05/19/2004
Place: Room 602
Abstract:
Streptococcus pyogenes is a significant human pathogen causing a wide spectrum of diseases ranging from uncomplicated infections to life-threatening toxic shock symptom and organ failure. The severe condition is associated with excessive vascular leakage. M protein, which can promote the survival of the bacterium in human blood, is one of the virulence factors of S. pyogenes. Several reports have indicated that M protein can bind fibrinogen (1). In this article, the authors tried to establish a correlation between M protein/fibrinogen complex and vascular leakage. They found that after S. pyogenes invaded the host, M proteins could be released from bacterial surface by neutrophil proteinases. The free M protein could then form complex with fibrinogen and bound b2 integrins of polymorphonuclear neutrophils (PMNs) (2) and activated these cells. The activated PMNs could release heparin binding protein, an inflammatory mediator inducing vascular leakage (3). The model was confirmed in vitro and in animal model. In addition, M protein/fibrinogen complexes were identified in tissue biopsies from a patient with severe S. pyogenes-caused necrotizing fasciitis, further underlining the pathogenic significance of such complex in severe streptococcal infections.
References:
1. Kantor, F. S. et al., 1965. Fibrinogen precipitation by streptococcal M protein. J. exp. Med. 121: 849–859.
2. Yan, S.R. et al., 1995. Activation of p58cfgr and p53/56lyn in adherent human neutrophils: evidence for a role of divalent cations in regulating neutrophils adhesion and protein tyrosine kinase activities. J. Inflamm. 45: 297-311.
3. Gautam, N. et al., 2001. Heparin-binding protein (HBP/CAP37): a missing link in neutrophil-evoked alteration of vascular permeability. Nat. Med. 7:1123 -1127.