Chen Chunsheng, Brown David R, Xie Yonghong, Green Benedict T, Lyte Mark
Department of Surgery, Minneapolis Medical Research Foundation/Hennepin County Medical Center, Minneapolis, Minnesota 55404, USA.
Shock. 2003 Aug;20(2):183-8. doi: 10.1097/01.shk.0000073867.66587.e0.
Enterohemorrhagic Escherichia coli O157:H7 (EHEC) is an important food-borne pathogen. While the molecular mechanisms governing E. coli O157:H7 pathogenesis have been intensively investigated, the role of host factors has received less attention. In this study, we tested the hypothesis that the enteric catecholamines norepinephrine (NE) and dopamine (DA) modulate interactions of the cecal mucosa with E. coli O157:H7. Full-thickness sheets of murine cecum were mounted in Ussing chambers and short circuit current and tissue electrical conductance were periodically determined to assess active transepithelial ion transport and ionic permeability, respectively. Neurochemicals and stationary-phase E. coli O157:H7 were exposed respectively to the contraluminal and luminal aspects of the mucosa. Epithelial adherence of E. coli O157:H7 was quantified by a bacterial adhesion assay after 90 min of luminal E. coli O157:H7 exposure. DA and NE increased E. coli O157:H7 adherence relative to untreated control tissues at 50% effective concentrations of 3.8 microM and 4.2 microM respectively. Pretreatment of tissues with either the alpha-adrenergic antagonist phentolamine or the beta-adrenergic antagonist propranolol prevented the action of NE. The effect of DA was prevented by the dopamine antagonist haloperidol. The drugs did not impair tissue viability or transepithelial conductance. The present findings suggest that enteric catecholamines modulate E. coli O157:H7 adherence to the cecal epithelium. Conditions associated with elevated catecholamine release, such as stress exposure, may influence host susceptibility to E. coli O157:H7 infection.
肠出血性大肠杆菌O157:H7（EHEC）是一种重要的食源性病原体。虽然已经对大肠杆菌O157:H7发病机制的分子机制进行了深入研究，但宿主因素的作用却较少受到关注。在本研究中，我们检验了这样一个假设，即肠道儿茶酚胺去甲肾上腺素（NE）和多巴胺（DA）调节盲肠黏膜与大肠杆菌O157:H7的相互作用。将小鼠盲肠的全层组织片安装在尤斯灌流小室中，定期测定短路电流和组织电导，分别评估主动跨上皮离子转运和离子通透性。将神经化学物质和静止期大肠杆菌O157:H7分别暴露于黏膜的对腔侧和腔侧。在向腔内暴露大肠杆菌O157:H7 90分钟后，通过细菌黏附试验对大肠杆菌O157:H7的上皮黏附进行定量。相对于未处理的对照组织，DA和NE分别在50%有效浓度为3.8 microM和4.2 microM时增加了大肠杆菌O157:H7的黏附。用α-肾上腺素能拮抗剂酚妥拉明或β-肾上腺素能拮抗剂普萘洛尔对组织进行预处理可阻止NE的作用。多巴胺拮抗剂氟哌啶醇可阻止DA的作用。这些药物不会损害组织活力或跨上皮电导。目前的研究结果表明，肠道儿茶酚胺调节大肠杆菌O157:H7对盲肠上皮的黏附。与儿茶酚胺释放增加相关的情况，如应激暴露，可能会影响宿主对大肠杆菌O157:H7感染的易感性。
