Persson T, Andersson P, Bodelsson M, Laurell M, Malm J, Egesten A
Sections for Medical Microbiology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden.
Infect Immun. 2001 Jun;69(6):3591-6. doi: 10.1128/IAI.69.6.3591-3596.2001.
Eosinophils participate in allergic inflammation and may have roles in the body's defense against helminthic infestation. Even under noninflammatory conditions, eosinophils are present in the mucosa of the large intestine, where large numbers of gram-negative bacteria reside. Therefore, roles for eosinophils in host defenses against bacterial invasion are possible. In a system for bacterial viable counts, the bactericidal activity of eosinophils and the contribution of different cellular antibacterial systems against Escherichia coli were investigated. Eosinophils showed a rapid and efficient killing of E. coli under aerobic conditions, whereas under anaerobic conditions bacterial killing decreased dramatically. In addition, diphenylene iodonium chloride (DPI), an inhibitor of the NADPH oxidase and thereby of superoxide production, also significantly inhibited bacterial killing. The inhibitor of nitric oxide (NO) production L-N(5)-(1-iminoethyl)-ornithine dihydrochloride did not affect the killing efficiency, suggesting that NO or derivatives thereof are of minor importance under the experimental conditions used. To investigate the involvement of superoxide and eosinophil peroxidase (EPO) in bacterial killing, EPO was blocked by azide. The rate of E. coli killing decreased significantly in the presence of azide, whereas addition of DPI did not further decrease the killing, suggesting that superoxide acts in conjunction with EPO. Bactericidal activity was seen in eosinophil extracts containing granule proteins, indicating that oxygen-independent killing may be of importance as well. The findings suggest that eosinophils can participate in host defense against gram-negative bacterial invasion and that oxygen-dependent killing, i.e., superoxide acting in conjunction with EPO, may be the most important bactericidal effector function of these cells.
嗜酸性粒细胞参与过敏性炎症反应,并且在机体抵御蠕虫感染中可能发挥作用。即使在非炎症条件下,嗜酸性粒细胞也存在于大量革兰氏阴性菌寄居的大肠黏膜中。因此,嗜酸性粒细胞在宿主抵御细菌入侵方面可能发挥作用。在一个细菌活菌计数系统中,研究了嗜酸性粒细胞的杀菌活性以及不同细胞抗菌系统对大肠杆菌的作用。嗜酸性粒细胞在有氧条件下能快速有效地杀灭大肠杆菌,而在厌氧条件下细菌杀灭率则显著下降。此外,二亚苯基碘鎓氯化物(DPI)是一种NADPH氧化酶抑制剂,因此也是超氧化物产生的抑制剂,它也能显著抑制细菌杀灭。一氧化氮(NO)产生的抑制剂L-N(5)-(1-亚氨基乙基)-鸟氨酸二盐酸盐并不影响杀灭效率,这表明在所用实验条件下,NO或其衍生物的重要性较低。为了研究超氧化物和嗜酸性粒细胞过氧化物酶(EPO)在细菌杀灭中的作用,用叠氮化物阻断EPO。在有叠氮化物存在的情况下,大肠杆菌的杀灭率显著下降,而添加DPI并没有进一步降低杀灭率,这表明超氧化物与EPO协同发挥作用。在含有颗粒蛋白的嗜酸性粒细胞提取物中观察到了杀菌活性,这表明非氧依赖的杀灭作用可能也很重要。这些发现表明,嗜酸性粒细胞可以参与宿主抵御革兰氏阴性菌入侵,并且氧依赖的杀灭作用,即超氧化物与EPO协同发挥作用,可能是这些细胞最重要的杀菌效应功能。