Staphylococcus aureus extracellular adherence protein serves as anti-inflammatory factor by inhibiting the recruitment of host leukocytes

Nat Med. 2002 Jul;8(7):687-93. doi: 10.1038/nm728. Epub 2002 Jun 24.


Staphylococcus aureus is a human pathogen that secretes proteins that contribute to bacterial colonization. Here we describe the extracellular adherence protein (Eap) as a novel anti-inflammatory factor that inhibits host leukocyte recruitment. Due to its direct interactions with the host adhesive proteins intercellular adhesion molecule 1 (ICAM-1), fibrinogen or vitronectin, Eap disrupted beta(2)-integrin and urokinase receptor mediated leukocyte adhesion in vitro. Whereas Eap-expressing S. aureus induced a 2 3-fold lower neutrophil recruitment in bacterial peritonitis in mice as compared with an Eap-negative strain, isolated Eap prevented beta(2)-integrin-dependent neutrophil recruitment in a mouse model of acute thioglycollate-induced peritonitis. Thus, the specific interactions with ICAM-1 and extracellular matrix proteins render Eap a potent anti-inflammatory factor, which may serve as a new therapeutic substance to block leukocyte extravasation in patients with hyperinflammatory pathologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Bacterial Adhesion*
  • Bacterial Proteins / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Line
  • Endothelium, Vascular / microbiology
  • Endothelium, Vascular / physiology
  • Fibronectins / physiology
  • Humans
  • Intercellular Adhesion Molecule-1 / physiology
  • Leukocytes / microbiology
  • Leukocytes / physiology*
  • Macrophage-1 Antigen / physiology
  • Mice
  • Mice, Inbred Strains
  • Peritonitis / microbiology
  • Peritonitis / prevention & control
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / prevention & control
  • Staphylococcus aureus / physiology*
  • U937 Cells
  • Umbilical Veins


  • Anti-Inflammatory Agents, Non-Steroidal
  • Bacterial Proteins
  • Fibronectins
  • Macrophage-1 Antigen
  • Intercellular Adhesion Molecule-1