Harris P R, Mobley H L, Perez-Perez G I, Blaser M J, Smith P D
Department of Pediatrics, University of Alabama School of Medicine, Birmingham, USA.
Gastroenterology. 1996 Aug;111(2):419-25. doi: 10.1053/gast.1996.v111.pm8690207.
BACKGROUND & AIMS: Helicobacter pylori surface proteins induce the production of proinflammatory mediators by mononuclear phagocytes, but the protein responsible for this stimulation has not been identified. This study determined whether urease, the major component of the soluble proteins extracted from H. pylori grown in culture, activates mononuclear phagocytes and stimulates them to produce proinflammatory cytokines.
Primary human blood monocytes were incubated with column-purified H. pylori urease and assayed by flow cytometry, Immunoassay, and reverse-transcription polymerase chain reaction for phenotypic, functional, and molecular evidence of activation.
H. pylori urease induced monocyte expression of surface interleukin 2 receptors and increased expression of HLA-DR, phenotypic changes consistent with activation. Urease also stimulated dose-dependent production of interleukin 1 beta, interleukin 6, interleukin 8, and tumor necrosis factor alpha peptides and messenger RNA. These urease-induced phenotypic and functional changes were inhibited by preincubation of the urease with antisera to H. pylori whole bacteria, purified urease, or the 31-kilodalton subunit of urease.
Among the soluble proteins released by H. pylori, urease is capable of activating monocytes for proinflammatory cytokines production. The local production of cytokines by urease-stimulated mononuclear phagocytes may play a central role in the development of H. pylori gastroduodenal inflammation.
幽门螺杆菌表面蛋白可诱导单核吞噬细胞产生促炎介质，但负责这种刺激的蛋白质尚未确定。本研究旨在确定脲酶（从培养的幽门螺杆菌中提取的可溶性蛋白的主要成分）是否能激活单核吞噬细胞并刺激其产生促炎细胞因子。
将原代人血单核细胞与经柱纯化的幽门螺杆菌脲酶孵育，通过流式细胞术、免疫测定和逆转录聚合酶链反应检测激活的表型、功能和分子证据。
幽门螺杆菌脲酶诱导单核细胞表面白细胞介素2受体表达，并增加HLA - DR表达，这些表型变化与激活一致。脲酶还刺激白细胞介素1β、白细胞介素6、白细胞介素8和肿瘤坏死因子α肽及信使核糖核酸的剂量依赖性产生。用抗幽门螺杆菌全菌、纯化脲酶或脲酶31千道尔顿亚基的抗血清预孵育脲酶可抑制这些由脲酶诱导的表型和功能变化。
在幽门螺杆菌释放的可溶性蛋白中，脲酶能够激活单核细胞产生促炎细胞因子。脲酶刺激的单核吞噬细胞局部产生细胞因子可能在幽门螺杆菌胃十二指肠炎症的发展中起核心作用。
