Hoque S S, Ghosh S, Poxton I R
Department of Medical Sciences, University of Edinburgh, UK.
Eur J Gastroenterol Hepatol. 2000 Nov;12(11):1185-93. doi: 10.1097/00042737-200012110-00004.
BACKGROUND/AIMS: Intestinal morphology has been shown to vary geographically. The impact of this variation on gut mucosal humoral immunity is not well-studied. The technique of peroral whole-gut lavage (WGL) with nonabsorbable cleansing fluid can be utilized for the study of gut immune responses in health and disease. In this study, the WGL technique was employed to compare various gut humoral immune parameters in healthy volunteers from Dhaka in Bangladesh and Edinburgh, UK.
Eleven healthy individuals (all male, age range 18-32) from Dhaka and 12 healthy individuals (4 male and 8 female, age range 23-48) from Edinburgh underwent WGL with a polyethylene glycol electrolyte-based solution drunk at a rate of 1 l/h. The first clear effluent was collected and processed. An ELISA technique was used to measure total immunoglobulins (A, M and G) and antibodies to bacterial lipopolysaccharide (LPS: endotoxin) ovalbumin and eotaxin. Immunoturbimetry and radioimmunoassy techniques were used to measure protein (albumin and alpha-1 antitrypsin) and eosinophil cationic protein (ECP), respectively, in WGL fluid (WGLF).
The total IgA, ECP and eotaxin concentrations in WGLF from the Dhaka group were significantly higher than those of the Edinburgh group (P < 0.03, P < 0.002 and P< 0.005 respectively). The IgA antibody level against the core oligosaccharide of bacterial LPS from several Gram-negative species was significantly higher in the Dhaka group compared to the Edinburgh group (P< 0.0001). Similarly, there was generally higher level of IgA antibody response against the various different LPS core structures of Escherichia coli in the Dhaka group, in particular significantly higher against R1, R3 and R4 LPS cores (P< 0.02, P< 0.03 and P< 0.01 respectively) compared to the Edinburgh group. In contrast to antibacterial antibodies, the IgA and IgM antibodies against ovalbumin were significantly lower in the Dhaka group (P< 0.001 and P< 0.003, respectively) compared to the Edinburgh group.
This study on gut mucosal humoral immunity from two geographically distinct populations suggests that place of residence influences gut mucosal humoral immunity. This difference in stimulation of humoral immunity of the gut might explain different rates of inflammatory bowel diseases in developing and developed countries, and also provides a major challenge for the development of mucosally presented vaccine worldwide.
背景/目的:肠道形态已被证明存在地域差异。这种差异对肠道黏膜体液免疫的影响尚未得到充分研究。口服不可吸收的清洁液进行全肠道灌洗(WGL)技术可用于研究健康和疾病状态下的肠道免疫反应。在本研究中,采用WGL技术比较了来自孟加拉国达卡和英国爱丁堡的健康志愿者的各种肠道体液免疫参数。
11名来自达卡的健康个体(均为男性,年龄范围18 - 32岁)和12名来自爱丁堡的健康个体(4名男性和8名女性,年龄范围23 - 48岁)接受了基于聚乙二醇电解质溶液的WGL,灌洗速度为1升/小时。收集并处理首次清亮的流出液。采用酶联免疫吸附测定(ELISA)技术测量总免疫球蛋白(A、M和G)以及针对细菌脂多糖(LPS:内毒素)、卵清蛋白和嗜酸性粒细胞趋化因子的抗体。分别采用免疫比浊法和放射免疫分析技术测量WGL液(WGLF)中的蛋白质(白蛋白和α-1抗胰蛋白酶)和嗜酸性粒细胞阳离子蛋白(ECP)。
达卡组WGLF中的总IgA、ECP和嗜酸性粒细胞趋化因子浓度显著高于爱丁堡组(分别为P < 0.03、P < 0.002和P < 0.005)。与爱丁堡组相比,达卡组中针对几种革兰氏阴性菌LPS核心寡糖的IgA抗体水平显著更高(P < 0.0001)。同样,与爱丁堡组相比,达卡组中针对大肠杆菌各种不同LPS核心结构的IgA抗体反应水平总体上更高,特别是针对R1、R3和R4 LPS核心的反应显著更高(分别为P < 0.02、P < 0.03和P < 0.01)。与抗菌抗体相反,达卡组中针对卵清蛋白的IgA和IgM抗体显著低于爱丁堡组(分别为P < 0.001和P < 0.003)。
这项针对两个地域不同人群的肠道黏膜体液免疫研究表明,居住地会影响肠道黏膜体液免疫。肠道体液免疫刺激的这种差异可能解释了发展中国家和发达国家炎症性肠病发病率的不同,也为全球黏膜疫苗的研发带来了重大挑战。