Extracellular gelsolin binds lipoteichoic acid and modulates cellular response to proinflammatory bacterial wall components
Extracellular gelsolin binds lipoteichoic acid and modulates cellular response to proinflammatory bacterial wall components
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DOI：
10.4049/jimmunol.181.7.4936
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发表时间：
2008-10-01
影响因子：
4.4
通讯作者：
Janmey, Paul A.
中科院分区：
文献类型：
--
作者：
Bucki, Robert;Byfield, Fitzroy J.;Janmey, Paul A.
凝胶在细胞外区室中的各种功能尚未明确定义，但包括肌动蛋白清除和抗炎作用。最近有报道称Gelsolin能以高亲和力结合多种革兰氏阴性菌的内毒素（LPS）。在这项研究中，我们研究了凝胶是否也与革兰氏阳性细菌的细菌壁分子相互作用，如二磷酸胆酸（LTA），以及凝胶与革兰氏阴性或革兰氏阳性细菌的细菌脂质的相互作用是否影响它们的细胞炎症反应。基于凝胶蛋白的PPI结合位点的肽（160-169）以与磷脂酰肌醇4,5-二磷酸相同的分子比例结合纯化的LTA。加入纯化的LTA后，发现重组人血浆凝胶的OD降低，凝胶与LTA的结合抑制了凝胶对f -肌动蛋白的解聚。同时，凝胶破坏了LTA激活NF-kappa B易位、e -选择素表达和中性粒细胞粘附于LTA处理的人主动脉内皮细胞的能力。Gelsolin能够部分抑制LPS或lta诱导的人中性粒细胞IL-8的释放，但不能阻止革兰氏阳性枯草芽孢杆菌或革兰氏阴性铜绿假单胞菌的生长，并且对抗菌肽衍生的抗菌肽LL37的抗菌活性没有影响。这些数据表明，细胞外凝胶参与宿主对LTA或LPS的免疫识别，这些分子在细胞分裂或受到药物和免疫成分的攻击时从细菌外膜释放出来。
The various functions of gelsolin in extracellular compartments are not yet clearly defined but include actin scavenging and antiinflammatory effects. Gelsolin was recently reported to bind endotoxin (LPS) from various Gram-negative bacteria with high affinity. In this study we investigate whether gelsolin also interacts with bacterial wall molecules of Gram-positive bacteria such as tipoteichoic acid (LTA) and whether gelsolin's interaction with bacterial lipids from Gram-negative or Gram-positive bacteria affects their cellular inflammatory responses. A peptide based on the PPI binding site of gelsolin (160-169) binds purified LTA at the same molecular ratio that it binds phosphatidylinositol 4,5-bisphosphate. The OD of recombinant human plasma gelsolin was found to decrease following the addition of purified LTA, and the binding of gelsolin to LTA inhibits F-actin depolymerization by gelsolin. Simultaneously, the ability of LTA to activate translocation of NF-kappa B, E-selectin expression, and adhesion of neutrophils to LTA-treated human aortic endothelial cells was compromised by gelsolin. Gelsolin was able to partially inhibit LPS- or LTA-induced release of IL-8 from human neutrophils but was unable to prevent Gram-positive Bacillus subtilis or Gram-negative Pseudomonas aeruginosa growth and had no effect on the antibacterial activity of the cathelicidin-derived antibacterial peptide LL37. These data suggest that extracellular gelsolin is involved in the host immune recognition of LTA or LPS following release of these molecules from the bacterial outer membrane during cell division or attack by drugs and immune components.