The extracellular adherence protein (Eap) of Staphylococcus aureus inhibits wound heating by interfering with host defense and repair mechanisms

被引:81
作者
Athanasopoulos, AN
Ecnomopoulou, M
Orlova, VV
Sobke, A
Schneider, D
Weber, H
Augustin, HG
Eming, SA
Schubert, U
Linn, T
Nawroth, PP
Hussain, MA
Hammes, HP
Herrmann, M
Preissner, KT
Chavakis, T
机构
[1] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA
[2] Heidelberg Univ, Dept Internal Med, D-6900 Heidelberg, Germany
[3] Univ Hosp Mannheim, Med Dept 5, Mannheim, Germany
[4] Univ Saarland, Inst Med Microbiol, D-6600 Saarbrucken, Germany
[5] Univ Giessen, Dept Internal Med, D-35390 Giessen, Germany
[6] Univ Giessen, Inst Biochem, D-35390 Giessen, Germany
[7] Res Tumor Biol Ctr, Dept Vasc Biol & Angiogenesis, Freiburg, Germany
[8] Univ Cologne, Dept Dermatol, D-5000 Cologne 41, Germany
[9] Univ Hosp Munster, Inst Med Microbiol, Munster, Germany
关键词
D O I
10.1182/blood-2005-08-3140
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 wild-type 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 intercellular adhesion molecule 1 (ICAM-1)-dependent leukocyte-endothelial interactions and diminished the consequent activation of the proinflammatory transcription factor nuclear factor kappa B (NF kappa B) in leukocytes associated with a decrease in expression of tissue factor. Moreover, Eap blocked alpha(v)-integrin-mediated endothelial-cell migration and capillary tube formation, and neovascularization in matrigels in vivo. Collectively, the potent anti-inflammatory and antiangiogenic 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 antiinflammatory and antiangiogenic therapies in several pathologies.
引用
收藏
页码:2720 / 2727
页数:8
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