Laarman, A.J. et al. (2012) Staphylococcus aureus Staphopain A inhibits CXCR2-dependent neutrophil activation and chemotaxis. EMBO Journal, 31(17), pp. 3607-3619. (doi: 10.1038/emboj.2012.212)
Full text not currently available from Enlighten.
Abstract
The CXC chemokine receptor 2 (CXCR2) on neutrophils, which recognizes chemokines produced at the site of infection, plays an important role in antimicrobial host defenses such as neutrophil activation and chemotaxis. Staphylococcus aureus is a successful human pathogen secreting a number of proteolytic enzymes, but their influence on the host immune system is not well understood. Here, we identify the cysteine protease Staphopain A as a chemokine receptor blocker. Neutrophils treated with Staphopain A are unresponsive to activation by all unique CXCR2 chemokines due to cleavage of the N-terminal domain, which can be neutralized by specific protease inhibitors. Moreover, Staphopain A inhibits neutrophil migration towards CXCR2 chemokines. By comparing a methicillin-resistant S. aureus (MRSA) strain with an isogenic Staphopain A mutant, we demonstrate that Staphopain A is the only secreted protease with activity towards CXCR2. Although the inability to cleave murine CXCR2 limits in-vivo studies, our data indicate that Staphopain A is an important immunomodulatory protein that blocks neutrophil recruitment by specific cleavage of the N-terminal domain of human CXCR2.
Item Type: | Articles |
---|---|
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Ward, Dr Richard and Milligan, Professor Graeme |
Authors: | Laarman, A.J., Mijnheer, G., Mootz, J.M., van Rooijen, W.J.M., Ruyken, M., Malone, C.L., Heezius, E.C., Ward, R., Milligan, G., van Strijp, J.A.G., de Haas, C.J.C., Horswill, A.R., van Kessel, K.P.M., and Rooijakkers, S.H.M. |
College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
Journal Name: | EMBO Journal |
ISSN: | 0261-4189 |
University Staff: Request a correction | Enlighten Editors: Update this record