Gyurko Robert, Boustany Gabriel, Huang Paul L, Kantarci Alpdogan, Van Dyke Thomas E, Genco Caroline A, Gibson Frank C
Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston University, Massachusetts 02118, USA.
Infect Immun. 2003 Sep;71(9):4917-24. doi: 10.1128/IAI.71.9.4917-4924.2003.
Porphyromonas gingivalis is a primary etiological agent of generalized severe periodontitis, and emerging data suggest the importance of reactive oxygen and nitrogen species in periodontal tissue damage, as well as in microbial killing. Since nitric oxide (NO) released from inducible NO synthase (iNOS) has been shown to possess immunomodulatory, cytotoxic, and antibacterial effects in experimental models, we challenged iNOS-deficient (iNOS(-/-)) mice with P. gingivalis by using a subcutaneous chamber model to study the specific contribution of NO to host defense during P. gingivalis infection. iNOS(-/-) mice inoculated with P. gingivalis developed skin lesions and chamber rejection with higher frequency and to a greater degree than similarly challenged C57BL/6 wild-type (WT) mice. Chamber fluid from iNOS(-/-) mice possessed significantly more P. gingivalis than that of WT mice. The immunoglobulin G responses to P. gingivalis in serum was similar in WT and iNOS(-/-) mice, and the inductions of tumor necrosis factor alpha, interleukin-1 beta and interleukin-6, and prostaglandin E(2) were comparable between the two mouse strains. Although no differences in total leukocyte counts in chamber fluids were observed between iNOS(-/-) and WT mice, the percentage of dead polymorphonuclear leukocytes (PMNs) was significantly greater in iNOS(-/-) mouse chamber fluids than that of WT samples. Interestingly, casein-elicited PMNs from iNOS(-/-) mice released more superoxide than did WT PMNs when stimulated with P. gingivalis. These results indicate that modulation of superoxide levels is a mechanism by which NO influences PMN function and that NO is an important element of the host defense against P. gingivalis.
牙龈卟啉单胞菌是广泛严重牙周炎的主要病原体，新出现的数据表明活性氧和氮物质在牙周组织损伤以及微生物杀灭中具有重要作用。由于在实验模型中，诱导型一氧化氮合酶（iNOS）释放的一氧化氮（NO）已显示出具有免疫调节、细胞毒性和抗菌作用，我们通过皮下腔室模型用牙龈卟啉单胞菌攻击iNOS缺陷（iNOS(-/-)）小鼠，以研究NO在牙龈卟啉单胞菌感染期间对宿主防御的具体作用。接种牙龈卟啉单胞菌的iNOS(-/-)小鼠比同样受到攻击的C57BL/6野生型（WT）小鼠出现皮肤病变和腔室排斥的频率更高、程度更严重。iNOS(-/-)小鼠的腔室液中牙龈卟啉单胞菌明显多于WT小鼠。WT和iNOS(-/-)小鼠血清中对牙龈卟啉单胞菌的免疫球蛋白G反应相似，两种小鼠品系中肿瘤坏死因子α、白细胞介素-1β和白细胞介素-6以及前列腺素E2的诱导情况相当。尽管在iNOS(-/-)和WT小鼠的腔室液中未观察到总白细胞计数有差异，但iNOS(-/-)小鼠腔室液中死亡多形核白细胞（PMN）的百分比明显高于WT样本。有趣的是，当用牙龈卟啉单胞菌刺激时，来自iNOS(-/-)小鼠的酪蛋白诱导的PMN释放的超氧化物比WT PMN更多。这些结果表明，超氧化物水平的调节是NO影响PMN功能的一种机制，并且NO是宿主抵御牙龈卟啉单胞菌的重要元素。
