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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2720-2727. Prepublished online as a Blood First Edition Paper on November 29, 2005; DOI 10.1182/blood-2005-08-3140. This Article Full Text (PDF) All Versions of this Article: 2005-08-3140v1 107/7/2720    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Athanasopoulos, A. N Articles by Chavakis, T. Search for Related Content PubMed PubMed Citation Articles by Athanasopoulos, A. N Articles by Chavakis, T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 4, 2005 Accepted November 14, 2005 The Extracellular Adherence Protein (Eap) of Staphylococcus aureus Inhibits Wound Healing by Interfering with Host Defense and Repair Mechanisms Athanasios N Athanasopoulos, Matina Economopoulou, Valeria V Orlova, Astrid Sobke, Darius Schneider, Holger Weber, Hellmut G Augustin, Sabine A Eming, Uwe Schubert, Thomas Linn, Peter P Nawroth, Muzaffar Hussain, Hans-Peter Hammes, Mathias Herrmann, Klaus T Preissner, and Triantafyllos Chavakis* Department of Internal Medicine, University Heidelberg, Heidelberg, Germany Experimental Immunology Branch, NCI NIH, Bethesda, MD, USA; Medical Department, University Hospital Mannheim, University Heidelberg, Mannheim, Germany Experimental Immunology Branch, NCI NIH, Bethesda, MD, USA Institute of Medical Microbiology, University of Saarland, Homburg/Saar, Germany Department of Internal Medicine, University Heidelberg, Heidelberg, Germany; Department of Internal Medicine, University Giessen, Giessen, Germany Department of Vascular Biology and Angiogenesis Research, Tumor Biology Center, Freiburg, Germany Department of Dermatology, University of Cologne, Cologne, Germany Institute for Biochemistry, University Giessen, Giessen, Germany Department of Internal Medicine, University Giessen, Giessen, Germany Institute of Medical Microbiology, University Hospital, Muenster, Germany Medical Department, University Hospital Mannheim, University Heidelberg, Mannheim, Germany * Corresponding author; email: chavakist{at}mail.nih.gov. Staphylococcus aureus is a major human pathogen interfering with host cell functions. Impaired wound healing is often observed in S. aureus infected wounds, yet, the underlying mechanisms are poorly defined. Here, we identify the extracellular adherence protein (Eap) of S. aureus to be responsible for impaired wound healing. In a mouse wound healing model wound closure was inhibited in the presence of wildtype S. aureus and this effect was reversible when the wounds were incubated with an isogenic Eap-deficient strain. Isolated Eap also delayed wound closure. In the presence of Eap, recruitment of inflammatory cells to the wound site as well as neovascularization of the wound were prevented. In vitro, Eap significantly reduced ICAM-1-dependent leukocyte-endothelial interactions and diminished the consequent activation of the pro-inflammatory transcription factor NFB in leukocytes associated with a decrease in expression of tissue factor. Moreover, Eap blocked v-integrin-mediated endothelial cell migration and capillary tube formation, and neovascularization in matrigels in vivo. Collectively, the potent anti-inflammatory and anti-angiogenic properties of Eap provide an underlying mechanism that may explain the impaired wound healing in S. aureus infected wounds. Eap may also serve as a lead compound for new anti-inflammatory and anti-angiogenic therapies in several pathologies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Johnson, A. Cockayne, and J. A. Morrissey Iron-Regulated Biofilm Formation in Staphylococcus aureus Newman Requires ica and the Secreted Protein Emp Infect. Immun., April 1, 2008; 76(4): 1756 - 1765. [Abstract] [Full Text] [PDF] M. Hussain, C. von Eiff, B. Sinha, I. Joost, M. Herrmann, G. Peters, and K. Becker eap Gene as Novel Target for Specific Identification of Staphylococcus aureus J. Clin. Microbiol., February 1, 2008; 46(2): 470 - 476. [Abstract] [Full Text] [PDF] N. Harraghy, D. Homerova, M. Herrmann, and J. Kormanec Mapping the Transcription Start Points of the Staphylococcus aureus eap, emp, and vwb Promoters Reveals a Conserved Octanucleotide Sequence That Is Essential for Expression of These Genes J. Bacteriol., January 1, 2008; 190(1): 447 - 451. [Abstract] [Full Text] [PDF] A. N. Athanasopoulos, D. Schneider, T. Keiper, V. Alt, U. R. Pendurthi, U. M. Liegibel, U. Sommer, P. P. Nawroth, C. Kasperk, and T. Chavakis Vascular Endothelial Growth Factor (VEGF)-induced Up-regulation of CCN1 in Osteoblasts Mediates Proangiogenic Activities in Endothelial Cells and Promotes Fracture Healing J. Biol. Chem., September 14, 2007; 282(37): 26746 - 26753. [Abstract] [Full Text] [PDF]

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