Fink Joshua, Mathaba Leslie T, Stewart Geoffrey A, Graham Peter T, Steer James H, Joyce David A, McWilliam Andrew S
School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Perth, Australia.
FEMS Immunol Med Microbiol. 2006 Mar;46(2):198-208. doi: 10.1111/j.1574-695X.2005.00022.x.
The outer membrane proteins of Moraxella catarrhalis, a bacterial pathogen which causes disease in both children and adults, play an important role in its phenotypic properties. However, their proinflammatory potential with regard to respiratory epithelium and macrophages is unclear. To this end, we examined the cytokine- and mediator-inducing capacity of a heat-killed wild-type M. catarrhalis strain and a nonautoagglutinating mutant as well as their outer membrane proteins and secretory/excretory products using the A549 respiratory epithelial cell line. The outer membrane proteins and secretory/excretory products from both isolates as well as the heat-killed bacteria all induced interleukin (IL)-6, IL-8 and prostaglandin E2, but not IL-1beta, from the A549 cell line in a dose- and time-dependent manner. Heat-killed bacteria and secretory/excretory products stimulated the release of IL-1beta, IL-6, IL-8 and prostaglandin E2 from human monocyte-derived macrophages. Both heat-killed isolates also stimulated nuclear translocation and transactivation of nuclear factor-kappaB. The heat-killed wild-type autoagglutinating isolate induced significantly greater amounts of IL-6 and IL-8 from A549 cells than the nonautoagglutinating mutant compared with the monocyte-derived macrophages but no significant differences in the amounts induced by the two strains were observed. These differences were also evident when the respiratory cell line was stimulated with outer membrane proteins as well as in the degree of nuclear factor-kappaB transactivation. There was little difference in the stimulatory activity of the secretory/excretory products. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analyses revealed some differences in the outer membrane proteins and secretory excretory products between the two isolates. Combined, these data show that M. catarrhalis secretory excretory products and outer membrane proteins are associated with the induction of inflammatory responses in both respiratory epithelium and macrophages.
卡他莫拉菌是一种可导致儿童和成人患病的细菌病原体，其外膜蛋白在其表型特性中发挥着重要作用。然而，它们对呼吸道上皮细胞和巨噬细胞的促炎潜力尚不清楚。为此，我们使用A549呼吸道上皮细胞系，检测了热灭活的野生型卡他莫拉菌菌株和非自凝突变体及其外膜蛋白和分泌/排泄产物诱导细胞因子和介质的能力。两种分离株的外膜蛋白、分泌/排泄产物以及热灭活细菌均以剂量和时间依赖性方式诱导A549细胞系产生白细胞介素（IL）-6、IL-8和前列腺素E2，但不诱导IL-1β。热灭活细菌和分泌/排泄产物刺激人单核细胞衍生巨噬细胞释放IL-1β、IL-6、IL-8和前列腺素E2。两种热灭活分离株还刺激核因子-κB的核转位和反式激活。与单核细胞衍生巨噬细胞相比，热灭活的野生型自凝分离株从A549细胞诱导产生的IL-6和IL-8量明显多于非自凝突变体，但未观察到两种菌株诱导量的显著差异。当用外膜蛋白刺激呼吸道细胞系时，这些差异也很明显，在核因子-κB反式激活程度上也是如此。分泌/排泄产物的刺激活性差异不大。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析显示，两种分离株在外膜蛋白和分泌排泄产物方面存在一些差异。综合这些数据表明，卡他莫拉菌的分泌排泄产物和外膜蛋白与呼吸道上皮细胞和巨噬细胞中炎症反应的诱导有关。
