Champagne C M, Holt S C, Van Dyke T E, Gordon B J, Shapira L
Department of Periodontology and Oral Biology, Goldman School of Graduate Dentistry, Boston University Medical Center, Massachusetts 02118, USA.
Oral Microbiol Immunol. 1996 Oct;11(5):319-25. doi: 10.1111/j.1399-302x.1996.tb00188.x.
One way prokaryotes respond to environmental stresses is by modifying selected outer membrane components. Iron, in the form of hemin, has been shown to be a significant regulator of Porphyromonas gingivalis growth and virulence and of the expression of outer membrane proteins and lipopoly saccharide. Since lipopoly saccharide has profound effects on host immune cells, this study compared the effect of hemin-restricted and hemin-normal P. gingivalis growth conditions on lipopolysaccharide priming of N-formylmethionyl-leucyl-phenylalanine-induced superoxide generation by human neutrophils. P. gingivalis was grown in a chemostat under normal (5 micrograms hemin/ml) and hemin-restricted (0.08 microgram hemin/ml) conditions. Purified lipopolysaccharide from both P. gingivalis normal and hemin-limited environments increased N-formylmethionyl-leucyl-phenylalanine-induced superoxide release by neutrophils in a dose-dependent manner. Lipopolysaccharide isolated from the hemin-normal conditions was a significantly more potent neutrophil priming agent than the lipopolysaccharide isolated from hemin-restricted conditions. Addition of normal human serum enhanced the priming effect of both lipopolysaccharide preparations; this effect, however, was more evident with the hemin-normal lipopolysaccharide. Further, this enhancing effect of serum was partly reduced in the presence of antibodies raised against the serum lipopolysaccharide-binding protein. The differences in the biological activity of the two lipopolysaccharide preparations could be associated with structural differences detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. These results indicate that hemin availability affects regulation of an aspect of P. gingivalis virulence, lipopolysaccharide-human neutrophils priming. The reduced capacity for neutrophil priming by hemin-restricted lipopolysaccharide appears to be related to lipopolysaccharide-neutrophil interactions and not to serum factors Targeting bacterial cell-surface components involved in hemin transport might be effective therapy for P. gingivalis-associated periodontal diseases.
原核生物应对环境压力的一种方式是改变特定的外膜成分。已证明,血红素形式的铁是牙龈卟啉单胞菌生长、毒力以及外膜蛋白和脂多糖表达的重要调节因子。由于脂多糖对宿主免疫细胞有深远影响,本研究比较了血红素限制和血红素正常的牙龈卟啉单胞菌生长条件对人中性粒细胞N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸诱导的超氧化物生成的脂多糖启动作用的影响。牙龈卟啉单胞菌在恒化器中于正常(5微克血红素/毫升)和血红素限制(0.08微克血红素/毫升)条件下培养。来自牙龈卟啉单胞菌正常和血红素限制环境的纯化脂多糖均以剂量依赖方式增加中性粒细胞对N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸诱导的超氧化物释放。从血红素正常条件下分离的脂多糖是比从血红素限制条件下分离的脂多糖显著更强的中性粒细胞启动剂。添加正常人血清增强了两种脂多糖制剂的启动作用;然而,这种作用在血红素正常的脂多糖中更明显。此外,在存在针对血清脂多糖结合蛋白产生的抗体时,血清的这种增强作用部分降低。两种脂多糖制剂生物活性的差异可能与通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析检测到的结构差异有关。这些结果表明,血红素的可利用性影响牙龈卟啉单胞菌毒力的一个方面,即脂多糖-人中性粒细胞启动的调节。血红素限制的脂多糖对中性粒细胞启动能力的降低似乎与脂多糖-中性粒细胞相互作用有关,而与血清因子无关。针对参与血红素转运的细菌细胞表面成分可能是治疗牙龈卟啉单胞菌相关牙周疾病的有效疗法。