Fujiwara Y, Arakawa T, Fukuda T, Sasaki E, Nakagawa K, Fujiwara K, Higuchi K, Kobayashi K, Tarnawski A
Third Department of Internal Medicine, Osaka City University Medical School, Japan.
Dig Dis Sci. 1997 Jun;42(6):1210-5. doi: 10.1023/a:1018850006714.
Acute Helicobacter pylori infection produces predominantly neutrophilic infiltration of the gastric mucosa. However, the precise mechanisms and mediators of neutrophil migration are not known. Interleukin-8 (IL-8), a potent chemotactic factor for neutrophils, is present at high concentration in the gastric mucosa of subjects with chronic gastritis caused by H. pylori infection. The aims of this study were to determine whether IL-8 stimulates polymorphonuclear leukocyte (PMN) migration across a cultured monolayer of rabbit gastric epithelial cells and whether PMN migration affects epithelial cell barrier function. Confluent gastric epithelial monolayers grown on the inserts were overlaid with PMNs and various amounts of IL-8 were administered into the well under the insert. Gastric epithelial barrier function was assessed by sodium back diffusion. IL-8 stimulated PMN migration across the monolayer in a dose- and time-dependent manner. PMN transmigration significantly increased sodium back diffusion. In conclusion, IL-8 induces PMN migration across a monolayer of cultured gastric epithelial cells. This IL-8 action is associated with impairment of gastric epithelial barrier function. Since H. pylori infection causes a local mucosal increase of IL-8, our present findings may explain the mechanism of H. pylori-induced PMN infiltration of the gastric glands and mucosal injury.
急性幽门螺杆菌感染主要导致胃黏膜中性粒细胞浸润。然而,中性粒细胞迁移的确切机制和介质尚不清楚。白细胞介素-8(IL-8)是一种对中性粒细胞有强大趋化作用的因子,在幽门螺杆菌感染引起的慢性胃炎患者的胃黏膜中浓度很高。本研究的目的是确定IL-8是否能刺激多形核白细胞(PMN)穿过培养的兔胃上皮细胞单层迁移,以及PMN迁移是否会影响上皮细胞屏障功能。将生长在小室上的汇合胃上皮单层覆盖PMN,并向小室下方的孔中加入不同量的IL-8。通过钠反向扩散评估胃上皮屏障功能。IL-8以剂量和时间依赖性方式刺激PMN穿过单层迁移。PMN跨膜迁移显著增加钠反向扩散。总之,IL-8诱导PMN穿过培养的胃上皮细胞单层迁移。这种IL-8作用与胃上皮屏障功能受损有关。由于幽门螺杆菌感染导致局部黏膜IL-8增加,我们目前的发现可能解释了幽门螺杆菌诱导胃腺PMN浸润和黏膜损伤的机制。