Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial antiinflammatory agent.
Leukocyte migration is a key event both in host defense against invading pathogens as well as in inflammation. Bacteria generate chemoattractants primarily by excretion (formylated peptides), complement activation (C5a), and subsequently through activation of leukocytes (e.g., leukotriene B4, platelet-activating factor, and interleukin 8). Here we describe a new protein secreted by Staphylococcus aureus that specifically impairs the response of neutrophils and monocytes to formylated peptides and C5a. This chemotaxis inhibitory protein of S. aureus (CHIPS) is a 14.1-kD protein encoded on a bacteriophage and is found in >60% of clinical isolates. CHIPS reduces the neutrophil recruitment toward C5a in a mouse peritonitis model, even though its activity is much more potent on human than on mouse cells. These findings suggest a new immune escape mechanism of S. aureus and put forward CHIPS as a potential new antiinflammatory therapeutic compound.
Eijkman-Winkler Institute, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Netherlands.
Carla J C
CJ
de Haas
Karin Ellen
KE
Veldkamp
Andreas
A
Peschel
Floor
F
Weerkamp
Willem J B
WJ
Van Wamel
Erik C J M
EC
Heezius
Miriam J J G
MJ
Poppelier
Kok P M
KP
Van Kessel
Jos A G
JA
van Strijp
D000595:Amino Acid Sequence; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology*; D001483:Base Sequence; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D015936:Complement C5a / Q000494:pharmacology; D004269:DNA, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D015936:Complement C5a