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首页> 外文期刊>Infection and immunity >Targeted Disruption of Fibronectin-Integrin Interactions in Human Gingival Fibroblasts by the RI Protease ofPorphyromonas gingivalis W50
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Targeted Disruption of Fibronectin-Integrin Interactions in Human Gingival Fibroblasts by the RI Protease ofPorphyromonas gingivalis W50

机译：牙龈卟啉单胞菌W50的RI蛋白酶靶向破坏人牙龈成纤维细胞中的纤连蛋白-整合素相互作用。

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Cell surface integrins mediate interactions between cells and their extracellular matrix and are frequently exploited by a range of bacterial pathogens to facilitate adherence and/or invasion. In this study we examined the effects of Porphyromonas gingivalisproteases on human gingival fibroblast (HGF) integrins and their fibronectin matrix. Culture supernatant from the virulent strain W50 caused considerably greater loss of the β1 integrin subunit from HGF in vitro than did that of the beige-pigmented strain W50/BE1. Prior treatment of the W50 culture supernatant with the protease inhibitor Nα-p-tosyl-l-lysine chloromethyl ketone (TLCK) blocked its effects on cultured cells, indicating that this process is proteolytically mediated. Purified arginine-specific proteases from P. gingivalis W50 were able to mimic the effects of the whole-culture supernatant on loss of β1 integrin expression. However purified RI, an α/β heterodimer in which the catalytic chain is associated with an adhesin chain, was 12 times more active than RIA, the catalytic monomer, in causing loss of the α5β1 integrin (fibronectin receptor) from HGF. No effect was observed on the αVβ3 integrin (vitronectin receptor). The sites of action of RI and RIA were investigated in cells exposed to proteases pretreated with TLCK to inactivate the catalytic component. Use of both monoclonal antibody 1A1, which recognizes only the adhesin chain of RI, and a rabbit antibody against P. gingivaliswhole cells indicated localization of RI on the fibroblasts in a clear, linear pattern typical of that seen with fibronectin and α5β1 integrin. Exact colocalization of RI with fibronectin and its α5β1 receptor was confirmed by double labeling and multiple-exposure photomicroscopy. In contrast, RIA bound to fibroblasts in a weak, patchy manner, showing only fine linear or granular staining. It is concluded that the adhesin component of RI targets the P. gingivalis arginine-protease to sites of fibronectin deposition on HGF, contributing to the rapid loss of both fibronectin and its main α5β1integrin receptor. Given the importance of integrin-ligand interactions in fibroblast function, their targeted disruption by RI may represent a novel mechanism of damage in periodontal disease.
机译：细胞表面整联蛋白介导细胞与其细胞外基质之间的相互作用，并经常被一系列细菌性病原体利用以促进粘附和/或侵袭。在这项研究中，我们研究了牙龈卟啉单胞菌蛋白酶对人牙龈成纤维细胞（HGF）整合素及其纤连蛋白基质的影响。与米色色素菌株W50 / BE1相比，毒性菌株W50的培养上清液在体外导致HGF中β 1 整合素亚基的损失明显更大。用蛋白酶抑制剂Nα- p -甲苯磺酰基-1-赖氨酸氯甲基酮（TLCK）预先处理W50培养上清液可阻断其对培养细胞的作用，表明该过程是蛋白水解介导的。来自 P的纯化的精氨酸特异性蛋白酶。牙龈炎W50能够模拟全培养上清液对β 1 整合素表达损失的影响。但是，纯化的RI（一种催化链与粘附素链相连的α/β异二聚体）的活性是催化单体RIA的12倍，导致α 5 β 1 整合素（纤连蛋白受体）。没有观察到对α V β 3 整联蛋白（玻连蛋白受体）的影响。在暴露于用TLCK预处理以灭活催化成分的蛋白酶的细胞中研究了RI和RIA的作用位点。使用仅识别RI粘附素链的单克隆抗体1A1和抗 P的兔抗体。牙龈整个细胞表明RI在成纤维细胞上的定位呈清晰，线性的模式，这与纤连蛋白和α 5 β 1 整合素所观察到的典型。双重标记和多次曝光显微镜证实了RI与纤连蛋白及其α 5 β 1 受体的精确共定位。相反，RIA以微弱的斑块状方式与成纤维细胞结合，仅显示出精细的线性或颗粒状染色。结论是RI的粘附素组分靶向 P。齿龈上的精氨酸蛋白酶使纤连蛋白沉积在HGF上，从而导致纤连蛋白及其主要的α 5 β 1 整合素受体迅速丢失。考虑到整联蛋白-配体相互作用在成纤维细胞功能中的重要性，它们对RI的靶向破坏可能代表了牙周疾病损害的新机制。

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