The Extracellular Adherence Protein from Staphylococcus Aureus Abrogates Angiogenic Responses of Endothelial Cells by Blocking Ras Activation.
From: Institute of Medical Microbiology and Hygiene, University of Saarland Hospital, D-66421 Homburg/Saar, Germany. astrid.sobke@gmx.de
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publish Date: Dec 2006
- ISSN: 1530-6860
- Volume: 20
- Issue: 14
- Pages: 2621-3
- Medium: Internet
- Language: English
- Citation (JAMA): Sobke Astrid C S, Selimovic Dennis, Orlova Valeria, et al. The Extracellular Adherence Protein from Staphylococcus Aureus Abrogates Angiogenic Responses of Endothelial Cells by Blocking Ras Activation.. FASEB J. Dec 2006;20:2621-3
Abstract
The extracellular adherence protein (Eap), a broad-spectrum adhesin secreted by Staphylococcus aureus, was previously shown to curb acute inflammatory responses, presumably through its binding to endothelial cell (EC) ICAM-1. Examining the effect of Eap on endothelial function in more detail, we here show that, in addition, Eap functions as a potent angiostatic agent. Concomitant treatment of EC with purified Eap resulted in the complete blockage of the mitogenic and sprouting responses elicited by vascular endothelial growth factor (VEGF)165 or basic fibroblast growth factor (bFGF). Moreover, the induction of tissue factor and decay-accelerating factor were repressed by Eap, as determined by qRT-polymerase chain reaction (qRT-PCR), with a corresponding reduction in Egr-1 protein up-regulation seen. This angiostatic activity was accompanied by a corresponding inhibition in ERK1/2 phosphorylation, while activation of p38 was not affected. Inhibition occurred downstream of tyrosine kinase receptor activation, as comparable effects were seen on TPA-induced ERK1/2 phosphorylation. Similar to previously described angiostatic agents like angiopoietin-1 or the 16-kDa prolactin fragment, Eap blockage of the Ras/Raf/MEK/ERK cascade was localized by pull-down assay at the level of Ras activation. Eap’s combined anti-inflammatory and antiangiogenic properties render this bacterial protein not only an important virulence factor during S. aureus infection but open new perspectives for therapeutic applications in pathological neovascularization.
Mesh Headings (Keywords): Bacterial Proteins, Cell Proliferation, Cells, Cultured, Endothelial Cells, Fibroblast Growth Factors, Humans, Mitogen-Activated Protein Kinase Kinases, Neovascularization, Physiologic, Phospholipase C gamma, Proto-Oncogene Proteins c-raf, RNA-Binding Proteins, Signal Transduction, Vascular Endothelial Growth Factor A, ras Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 17077291
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