Activation of human polymorphonuclear neutrophils by streptolysin O from Streptococcus pyogenes leads to the release of proinflammatory mediators

Thromb Haemost. 2006 Jun;95(6):982-90. doi: 10.1160/TH05-08-0572.

Abstract

Streptococcus pyogenes is an important Gram-positive pathogen that is strictly limited to infections in humans. Here we report that streptolysin O (SLO), a cytolytic exotoxin secreted by S. pyogenes, activates human polymorphonuclear neutrophils (PMNs) by perforating these cells. This appears to be followed by an influx of Ca(2+) and p38 MAPK activation. As a consequence, PMNs secrete heparin-binding protein, a potent inducer of vascular leakage, and neutrophil-borne proteins, including LL-37, alpha-defensins, and elastase. The results of the present work therefore suggest that the interaction between SLO and PMNs evokes an exaggerated host response which may contribute to the pathogenesis of local and generalized S. pyogenes infections.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimicrobial Cationic Peptides / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Blood Proteins / metabolism
  • Calcium / metabolism
  • Carrier Proteins / metabolism
  • Cathelicidins
  • Cell Degranulation*
  • Chelating Agents / pharmacology
  • Egtazic Acid / pharmacology
  • Erythrocytes / metabolism
  • Hemolysis
  • Humans
  • Imidazoles / pharmacology
  • Inflammation Mediators / metabolism*
  • Mutation
  • Neutrophils / drug effects
  • Neutrophils / microbiology
  • Neutrophils / physiology*
  • Neutrophils / ultrastructure
  • Protein Kinase Inhibitors / pharmacology
  • Pyridines / pharmacology
  • Signal Transduction
  • Streptococcus pyogenes / enzymology*
  • Streptococcus pyogenes / genetics
  • Streptococcus pyogenes / isolation & purification
  • Streptolysins / genetics
  • Streptolysins / metabolism*
  • Transfection
  • alpha-Defensins / metabolism
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • AZU1 protein, human
  • Antimicrobial Cationic Peptides
  • Bacterial Proteins
  • Blood Proteins
  • Carrier Proteins
  • Chelating Agents
  • Imidazoles
  • Inflammation Mediators
  • Protein Kinase Inhibitors
  • Pyridines
  • Streptolysins
  • alpha-Defensins
  • streptolysin O
  • Egtazic Acid
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580
  • Calcium
  • Cathelicidins