Staphylococcus aureus extracellular adherence protein serves as anti-inflammatory factor by inhibiting the recruitment of host leukocytes.
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.
Chavakis
Triantafyllos
T
Institute for Biochemistry, Third Department of Internal Medicine, Justus-Liebig-Universität, Giessen, Germany. triantafyllos.chavakis@innere.med.uni-giessen.de
Hussain
Muzaffar
M
Kanse
Sandip M
SM
Peters
Georg
G
Bretzel
Reinhard G
RG
Flock
Jan-Ingmar
JI
Herrmann
Mathias
M
Preissner
Klaus T
KT
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004730:Endothelium, Vascular / Q000382:microbiology / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007962:Leukocytes / Q000382:microbiology / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D010538:Peritonitis / Q000382:microbiology / Q000517:prevention & control; D013203:Staphylococcal Infections / Q000382:microbiology / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000502:physiology*; D020298:U937 Cells; D014471:Umbilical Veins
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001426:Bacterial Proteins; D005353:Fibronectins; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1