Isomoto Hajime, Mukae Hiroshi, Ishimoto Hiroshi, Nishi Yoshito, Wen Chun-Yang, Wada Akihiro, Ohnita Ken, Hirayama Toshiya, Nakazato Masamitsu, Kohno Shigeru
Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
World J Gastroenterol. 2005 Aug 21;11(31):4782-7. doi: 10.3748/wjg.v11.i31.4782.
Human beta-defensin (HBD)-1 and HBD-2 are endogenous antimicrobial peptides. Unlike HBD-1, the HBD-2 expression is augmented by Helicobacter pylori (H pylori). We sought to determine HBD-1 and HBD-2 concentrations in gastric juice during H pylori infection.
HBD-1 and HBD-2 concentrations were measured by radioimmunoassay in plasma and gastric juice of 49 H pylori-infected and 33 uninfected subjects and before and after anti-H pylori treatment in 13 patients with H pylori-associated gastritis. Interleukin (IL)-1beta and IL-8 concentrations in gastric juice were measured by enzyme-linked immunosorbent assay (ELISA). Histological grades of gastritis were determined using two biopsy specimens taken from the antrum and corpus. Reverse phase high performance liquid chromatography (RP-HPLC) was used to identify HBD-2.
HBD-2 concentrations in gastric juice, but not in plasma, were significantly higher in H pylori-positive than -negative subjects, albeit the post-treatment levels were unchanged. Immunoreactivity for HBD-2 was exclusively identified in H pylori-infected mucosa by RP-HPLC. HBD-2 concentrations in gastric juice correlated with histological degree of neutrophil and mononuclear cell infiltration in the corpus. IL-1beta levels correlated with those of IL-8, but not HBD-2. Plasma and gastric juice HBD-1 concentrations were similar in H pylori-infected and uninfected subjects.
Our results place the beta-defensins, especially HBD-2, in the front line of innate immune defence. Moreover, HBD-2 may be involved in the pathogenesis of H pylori-associated gastritis, possibly through its function as immune and inflammatory mediator.
人β-防御素(HBD)-1和HBD-2是内源性抗菌肽。与HBD-1不同,幽门螺杆菌(Hp)可增强HBD-2的表达。我们试图确定幽门螺杆菌感染期间胃液中HBD-1和HBD-2的浓度。
采用放射免疫分析法测定49例幽门螺杆菌感染患者和33例未感染患者血浆和胃液中HBD-1和HBD-2的浓度,并对13例幽门螺杆菌相关性胃炎患者进行抗幽门螺杆菌治疗前后的检测。采用酶联免疫吸附测定法(ELISA)测定胃液中白细胞介素(IL)-1β和IL-8的浓度。使用取自胃窦和胃体的两个活检标本确定胃炎的组织学分级。采用反相高效液相色谱法(RP-HPLC)鉴定HBD-2。
幽门螺杆菌阳性患者胃液中HBD-2浓度显著高于阴性患者,血浆中则无此差异,尽管治疗后水平未变。通过RP-HPLC仅在幽门螺杆菌感染的黏膜中鉴定出HBD-2的免疫反应性。胃液中HBD-2浓度与胃体中嗜中性粒细胞和单核细胞浸润的组织学程度相关。IL-1β水平与IL-8水平相关,但与HBD-2无关。幽门螺杆菌感染患者和未感染患者血浆和胃液中HBD-1浓度相似。
我们的结果表明β-防御素,尤其是HBD-2,处于天然免疫防御的第一线。此外,HBD-2可能参与幽门螺杆菌相关性胃炎的发病机制,可能是通过其作为免疫和炎症介质的功能。