Department of Physiological Sciences, Stellenbosch University, Stellenbosch, Private Bag X1 Matieland, 7602, South Africa.
Central Analytical Facilities, Fluorescence Microscopy Unit, Stellenbosch University, Stellenbosch, Private Bag X1 Matieland, 7602, South Africa.
Sci Rep. 2018 Nov 14;8(1):16798. doi: 10.1038/s41598-018-35009-y.
Many chronic diseases, including those classified as cardiovascular, neurodegenerative, or autoimmune, are characterized by persistent inflammation. The origin of this inflammation is mostly unclear, but it is typically mediated by inflammatory biomarkers, such as cytokines, and affected by both environmental and genetic factors. Recently circulating bacterial inflammagens such as lipopolysaccharide (LPS) have been implicated. We used a highly selective mouse monoclonal antibody to detect bacterial LPS in whole blood and/or platelet poor plasma of individuals with Parkinson's Disease, Alzheimer's type dementia, or Type 2 Diabetes Mellitus. Our results showed that staining is significantly enhanced (P < 0.0001) compared to healthy controls. Aberrant blood clots in these patient groups are characterized by amyloid formation as shown by the amyloid-selective stains thioflavin T and Amytracker™ 480 or 680. Correlative Light-Electron Microscopy (CLEM) illustrated that the LPS antibody staining is located in the same places as where amyloid fibrils may be observed. These data are consistent with the Iron Dysregulation and Dormant Microbes (IDDM) hypothesis in which bacterial inflammagens such as LPS are responsible for anomalous blood clotting as part of the aetiology of these chronic inflammatory diseases.
许多慢性疾病，包括心血管疾病、神经退行性疾病和自身免疫性疾病，其特征是持续存在炎症。这种炎症的起源大多不清楚，但通常由炎症生物标志物（如细胞因子）介导，并受环境和遗传因素的影响。最近，循环细菌内毒素（如脂多糖 [LPS]）已被认为与此有关。我们使用一种高度选择性的小鼠单克隆抗体来检测帕金森病、阿尔茨海默病型痴呆或 2 型糖尿病患者的全血和/或血小板贫血浆中的细菌 LPS。我们的结果表明，与健康对照组相比，染色显著增强（P<0.0001）。这些患者群体中的异常血栓形成的特征是淀粉样蛋白形成，如淀粉样蛋白选择性染色试剂硫黄素 T 和 Amytracker™480 或 680 所示。相关光电子显微镜（CLEM）表明，LPS 抗体染色与可能观察到淀粉样纤维的位置相同。这些数据与铁失调和休眠微生物（IDDM）假说一致，该假说认为 LPS 等细菌内毒素是导致这些慢性炎症性疾病病因学中异常凝血的原因之一。
