School of Biological Sciences.
J Infect Dis. 2013 Dec 15;208(12):2046-57. doi: 10.1093/infdis/jit398. Epub 2013 Aug 2.
Impaired healing is common in wounds infected with the major human pathogen Staphylococcus aureus, although the underlying mechanisms are poorly understood. Here, we show that S. aureus lipoteichoic acid (LTA) inhibits platelet aggregation caused by physiological agonists and S. aureus and reduced platelet thrombus formation in vitro. The presence of D-alanine on LTA is necessary for the full inhibitory effect. Inhibition of aggregation was blocked using a monoclonal anti-platelet activating factor receptor (PafR) antibody and Ginkgolide B, a well-defined PafR antagonist, demonstrating that the LTA inhibitory signal occurs via PafR. Using a cyclic AMP (cAMP) assay and a Western blot for phosphorylated VASP, we determined that cAMP levels increase upon platelet incubation with LTA, an effect which inhibits platelet activation. This was blocked when platelets were preincubated with Ginkgolide B. Furthermore, LTA reduced hemostasis in a mouse tail-bleed assay.
金黄色葡萄球菌感染导致的伤口愈合受损很常见，尽管其潜在机制尚不清楚。在这里，我们发现金黄色葡萄球菌的脂磷壁酸（LTA）可抑制生理激动剂和金黄色葡萄球菌引起的血小板聚集，并减少体外血小板血栓形成。LTA 上 D-丙氨酸的存在对于完全抑制作用是必需的。使用单克隆抗血小板激活因子受体（PafR）抗体和银杏内酯 B（一种明确的 PafR 拮抗剂）阻断聚集抑制，表明 LTA 的抑制信号通过 PafR 发生。通过 cAMP 测定和磷酸化 VASP 的 Western blot，我们确定血小板与 LTA 孵育时 cAMP 水平增加，这一效应抑制血小板活化。当血小板用银杏内酯 B 预孵育时，这种作用被阻断。此外，LTA 减少了小鼠尾巴出血试验中的止血作用。
