Department of Laboratory Medicine, Division of Medical Microbiology, Lund University, Sölvegatan 23, Lund, Sweden.
Appl Biochem Biotechnol. 2011 May;164(1):1-9. doi: 10.1007/s12010-010-9109-7. Epub 2010 Nov 19.
Helicobacter species have been isolated and cultured from both the gastric and enterohepatic niches of the gastrointestinal tract and are associated with a wide spectrum of diseases. Some members of the enterohepatic Helicobacter species (EHS), which include Helicobacter bilis, Helicobacter hepaticus and Helicobacter pullorum, are associated with chronic inflammatory and proliferative bowel inflammation, hepatitis and in experimental murine studies with hepatic cancer. The present study aimed to explore if polysulphated polysaccharides can prevent adhesion of EHS to the murine macrophage cell line J774A.1. A competitive binding assay showed that heparin and heparan sulphate at a concentration of 1.25 mg/ml reduced binding of H. hepaticus and H. pullorum to the host cells, but not H. bilis. Of the tested Helicobacter spp, the highest inhibition by heparin was demonstrated for H. pullorum (P < 0.01), the most hydrophilic strain. Partially or completely de-sulphated heparin derivatives lost the ability to inhibit adherence of EHS, indicating the importance of sulphated groups of heparin. The most efficient inhibitor of EHS binding to macrophages was fucoidan, which reduced bacterial adhesion of the three enterohepatic Helicobacter species to a greater extent than heparin, 60-90% inhibition vs 30-70% inhibition by heparin. Identification of receptors that EHS ligands bind to is important for understanding the development of infection and may provide a rational target to prevent infection and therapy.
幽门螺旋杆菌已从胃肠道的胃和肠肝两个生态位中分离和培养出来，并与广泛的疾病相关。一些肠肝幽门螺旋杆菌（EHS）成员，包括胆螺旋杆菌、肝螺旋杆菌和鸡螺旋杆菌，与慢性炎症性和增殖性肠炎、肝炎以及实验性肝癌的小鼠研究有关。本研究旨在探索多硫酸化多糖是否可以预防 EHS 与鼠巨噬细胞系 J774A.1 的黏附。竞争结合测定表明，肝素和硫酸乙酰肝素在 1.25mg/ml 的浓度下可降低 H. hepaticus 和 H. pullorum 对宿主细胞的结合，但不能降低 H. bilis 的结合。在所测试的 Helicobacter spp 中，肝素对亲水性最强的 H. pullorum 的抑制作用最高（P<0.01）。部分或完全去硫酸化的肝素衍生物丧失了抑制 EHS 黏附的能力，表明肝素硫酸基团的重要性。对巨噬细胞中 EHS 结合的最有效抑制剂是褐藻聚糖，它降低了三种肠肝幽门螺旋杆菌的细菌黏附，抑制程度比肝素高 60-90%，比肝素高 30-70%。鉴定 EHS 配体结合的受体对于了解感染的发展非常重要，并且可能为预防感染和治疗提供合理的靶点。
