| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Eijkman Winkler Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands; and
Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
Staphylococcus aureus excretes a factor that specifically and simultaneously acts on the C5aR and the formylated peptide receptor (FPR). This chemotaxis inhibitory protein of S. aureus (CHIPS) blocks C5a- and fMLP-induced phagocyte activation and chemotaxis. Monoclonal anti-CHIPS Abs inhibit CHIPS activity against one receptor completely without affecting the other receptor, indicating that two distinct sites are responsible for both actions. A CHIPS-derived N-terminal 6 aa peptide is capable of mimicking the anti-FPR properties of CHIPS but has no effect on the C5aR. Synthetic peptides in which the first 6 aa are substituted individually for all other naturally occurring amino acids show that the first and third residue play an important role in blocking the FPR. Using an Escherichia coli expression system, we created mutant CHIPS proteins in which these amino acids are substituted. These mutant proteins have impaired or absent FPR- but still an intact C5aR-blocking activity, indicating that the loss of the FPR-blocking activity is not caused by any structural impairment. This identifies the first and third amino acid, both a phenylalanine, to be essential for CHIPS blocking the fMLP-induced activation of phagocytes. The unique properties of CHIPS to specifically inhibit the FPR with high affinity (kd = 35.4 ± 7.7 nM) could be an important new tool to further stimulate the fundamental research on the mechanisms underlying the FPR and its role in disease processes.
This article has been cited by other articles:
|
|
 |
|
  C. Prat, P.-J. Haas, J. Bestebroer, C. J. C. de Haas, J. A. G. van Strijp, and K. P. M. van Kessel A Homolog of Formyl Peptide Receptor-Like 1 (FPRL1) Inhibitor from Staphylococcus aureus (FPRL1 Inhibitory Protein) That Inhibits FPRL1 and FPR J. Immunol., November 15, 2009; 183(10): 6569 - 6578. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Ye, F. Boulay, J. M. Wang, C. Dahlgren, C. Gerard, M. Parmentier, C. N. Serhan, and P. M. Murphy International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the Formyl Peptide Receptor (FPR) Family Pharmacol. Rev., June 1, 2009; 61(2): 119 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bestebroer, K. P. M. van Kessel, H. Azouagh, A. M. Walenkamp, I. G. J. Boer, R. A. Romijn, J. A. G. van Strijp, and C. J. C. de Haas Staphylococcal SSL5 inhibits leukocyte activation by chemokines and anaphylatoxins Blood, January 8, 2009; 113(2): 328 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. M. Rooijakkers, F. J. Milder, B. W. Bardoel, M. Ruyken, J. A. G. van Strijp, and P. Gros Staphylococcal Complement Inhibitor: Structure and Active Sites J. Immunol., September 1, 2007; 179(5): 2989 - 2998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. B. van Wamel, S. H. M. Rooijakkers, M. Ruyken, K. P. M. van Kessel, and J. A. G. van Strijp The Innate Immune Modulators Staphylococcal Complement Inhibitor and Chemotaxis Inhibitory Protein of Staphylococcus aureus Are Located on {beta}-Hemolysin-Converting Bacteriophages J. Bacteriol., February 15, 2006; 188(4): 1310 - 1315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Postma, W. Kleibeuker, M. J. J. G. Poppelier, M. Boonstra, K. P. M. Van Kessel, J. A. G. Van Strijp, and C. J. C. de Haas Residues 10-18 within the C5a Receptor N Terminus Compose a Binding Domain for Chemotaxis Inhibitory Protein of Staphylococcus aureus J. Biol. Chem., January 21, 2005; 280(3): 2020 - 2027. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
