Helicobacter pylori Lipopolysaccharides Preferentially Induce CXC Chemokine Production in Human Monocytes

Helicobacter pylori infection can cause duodenal ulcers and may also induce gastric adenocarcinoma. The bacteria colonize the gastric mucosa and areas of gastric metaplasia in the duodenum for decades, resulting in active chronic inflammation in the infected areas. A characteristic feature of the infection is the ongoing recruitment of neutrophils to the infected sites. To evaluate the role of H. pylori lipopolysaccharides (LPS) in the recruitment of leukocytes to the gastric mucosa, we have examined the cytokine and chemokine production from human monocytes stimulated with LPS isolated from different H. pylori strains, as well as from several other gram-negative bacteria. Our results show that H. pylori LPS induce a large production of neutrophil-recruiting CXC chemokines (interleukin-8 and growth-related oncogene alpha) from purified human monocytes, to almost the same extent as Escherichia coli LPS. However, and in agreement with previous studies, H. pylori LPS was much less potent in inducing production of proinflammatory cytokines by purified human monocytes and was also a weak inducer of the CC chemokine RANTES. There was no difference between LPS preparations from different H. pylori strains in their ability to induce cytokines and chemokines. The preferential production of CXC chemokines after stimulation with H. pylori LPS indicates an important contribution of this molecule in maintaining neutrophil recruitment during the infection, irrespective of the infecting strain.

幽门螺杆菌（Helicobacter pylori）感染可引发十二指肠溃疡，还可能诱导胃腺癌发生。该细菌可在胃黏膜及十二指肠内的胃化生区域定植数十年，导致感染部位出现活动性慢性炎症。此类感染的特征性表现为中性粒细胞持续向感染部位募集。为评估幽门螺杆菌脂多糖（lipopolysaccharides, LPS）在白细胞向胃黏膜募集过程中的作用，我们检测了不同幽门螺杆菌菌株及其他数株革兰氏阴性菌来源的LPS刺激人单核细胞后产生的细胞因子与趋化因子水平。结果显示，幽门螺杆菌LPS可从纯化人单核细胞中诱导大量趋化中性粒细胞的CXC趋化因子（白细胞介素8与生长相关癌基因α）产生，其效果与大肠埃希菌（Escherichia coli）LPS几乎相当。然而，与既往研究结果一致的是，幽门螺杆菌LPS诱导纯化人单核细胞产生促炎细胞因子的能力远弱于后者，同时其作为CC趋化因子RANTES的诱导剂活性也较弱。不同幽门螺杆菌菌株来源的LPS在诱导细胞因子与趋化因子的能力上并无差异。幽门螺杆菌LPS刺激后优先产生CXC趋化因子，这表明该分子在感染期间维持中性粒细胞募集的过程中发挥了重要作用，且与感染菌株类型无关。