Syndecan-1 as a mediator of bacteria-enterocyte interactions.
Syndecan-1 as a mediator of bacteria-enterocyte interactions.
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DOI：
10.1100/tsw.2006.100
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发表时间：
2006-04-14
影响因子：
--
通讯作者：
Wells CL
中科院分区：
文献类型：
--
作者：
Henry-Stanley M;Wells CL
正常肠道细菌经常引起免疫抑制和术后患者以及休克和创伤患者的并发感染。许多医院感染的病灶不明确，似乎是由正常肠道细菌移位引起的，这些细菌以某种方式穿透肠上皮并进入无菌的肠外组织[1，2，3]。尽管进行了适当的抗菌治疗，相关死亡率通常较高（20-40%）[2，4]。因此，阐明正常肠植物群穿透肠上皮的机制是重要的，因为抗生素治疗通常无效，并且因为新的知识可能提示新的预防和治疗剂以降低与易位肠植物群相关的昂贵的发病率。多种临床病症与正常肠道细菌穿过肠上皮屏障的通道增加相关。这些病症包括肠道微生物过度生长、肠道萎缩、流质饮食、肠道停滞、缺血-再灌注损伤、免疫抑制、手术、烧伤、休克、创伤和循环内毒素增加。这些不同的病症与肠上皮通透性增加相关，促进基底外侧肠上皮细胞表面的暴露，通常通过紧密连接连接，防止微生物和不需要的大分子的细胞旁通过（综述见[1]）。基于许多细菌的内化在基底外侧是有利的证据，在极化上皮细胞的基底外侧表面（与顶端相反）[5，6]，我们最近测试了多配体蛋白聚糖-1（一种硫酸乙酰肝素（HS）蛋白聚糖（PG））在基底外侧上皮表面显著表达的假设[7，8]，可能参与正常肠道细菌与宿主肠细胞的相互作用[9]。多配体蛋白聚糖是广泛表达的跨膜PG的四个家族（多配体蛋白聚糖-1、-2、-3、-4）。每个多配体聚糖核心蛋白具有跨膜部分、相对短的胞质内区域和用三至五个糖胺聚糖（GAG）链修饰的胞外结构域[10，11]。多配体蛋白聚糖-1（图1）、多配体蛋白聚糖-3和多配体蛋白聚糖-4的胞外结构域可携带HS和硫酸软骨素（CS）GAG链，而多配体蛋白聚糖-2似乎仅表达HS [10，12]。Syndecan-1主要/主要在上皮细胞上表达，并且可以在发育期间在间充质中发现。多配体蛋白聚糖-2在间充质组织中以及在肝和神经元细胞中是突出的。Syndecan-3与神经组织相关，syndecan-4广泛分布在许多细胞类型中[10，13]。多配体聚糖可以结合生长因子、趋化因子、细胞因子、细胞外基质成分、凝血级联的组分和各种微生物[14，15]，并且许多优雅的综述描述了多配体聚糖结构和功能的方面[10，11，14，16]。
Normal enteric bacteria frequently cause complicating infections in immunosuppressed and postsurgical patients, as well as patients with shock and trauma. Many nosocomial infections have an undefined focus and appear to be caused by translocating normal enteric bacteria that somehow penetrate the intestinal epithelium and enter otherwise sterile extraintestinal tissues [1, 2, 3]. Associated mortality is often high (20–40%) despite appropriate antimicrobial therapy [2, 4]. Thus, clarification of the mechanisms by which normal enteric flora penetrate the intestinal epithelium is important because antibiotic therapy is often ineffective and because new knowledge may suggest novel prophylactic and therapeutic agents to decrease the costly morbidity associated with translocating enteric flora. A variety of clinical conditions are associated with increased passage of normal enteric bacteria across the intestinal epithelial barrier. These conditions include enteric microbial overgrowth, gut atrophy, liquid diet, gut stasis, ischemia-reperfusion injury, immunosuppression, surgery, burn wounds, shock, trauma, and increased circulating endotoxin. These diverse conditions are associated with increased intestinal epithelial permeability, facilitating exposure of basolateral enterocyte surfaces, normally joined by tight junctions that prevent the paracellular passage of microbes and unwanted macromolecules (reviewed in [1]). Based on evidence that internalization of a number of bacteria is favored at the basolateral (as opposed to apical) surface of polarized epithelial cells [5, 6], we recently tested the hypothesis that syndecan-1, a heparan sulfate (HS) proteoglycan (PG) prominently expressed on the basolateral epithelial surface [7, 8], may be involved in interactions of normal enteric bacteria with host enterocytes [9].The syndecans are a family of four (syndecan-1,-2,-3,-4) widely expressed transmembrane PGs. Each syndecan core protein has a transmembrane portion, a relatively short intracytoplasmic region, and an extracellular domain decorated with three to five glycosaminoglycan (GAG) chains [10, 11]. Ectodomains of syndecan-1 (Fig. 1),-3, and-4 may bear both HS and chondroitin sulfate (CS) GAG chains, while syndecan-2 appears to express only HS [10, 12]. Syndecan-1 is mainly/predominantly expressed on epithelia and may be found in the mesenchyme during development. Syndecan-2 is prominent in mesenchymal tissues, and on liver and neuronal cells. Syndecan-3 is associated with neural tissues and syndecan-4 is widely distributed in many cell types [10, 13]. Syndecans can bind growth factors, chemokines, cytokines, extracellular matrix constituents, components of the coagulation cascade, and various microbes [14, 15], and a number of elegant reviews describe aspects of syndecan structure and function [10, 11, 14, 16].
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