Caronzolo Dario, Lucini Valeria, Pannacci Marilou, Grosso Silvia, Kieffer Nelly, Bello Lorenzo, Bikfalvi Andreas, Scaglione Francesco
Department of Pharmacology, Chemotherapy, and Toxicology, University of Milan, Milan, Italy.
Antimicrob Agents Chemother. 2006 Oct;50(10):3277-82. doi: 10.1128/AAC.00108-06.
Chlamydophila pneumoniae is a pathogen that is involved in acute and chronic respiratory infections and that is associated with asthma and coronary artery diseases. In this study, we evaluated the effects of PEX, a noncatalytic metalloproteinase fragment with integrin-binding activity, against experimental infections caused by C. pneumoniae. Moreover, we investigated the relationships between C. pneumoniae and alpha(v)beta(3) integrin functions in order to explain the possible mechanism of action of PEX both in vitro and in vivo. For the in vitro experiments, HeLa cells were infected with C. pneumoniae and treated with either PEX or azithromycin. The results obtained with PEX were not significantly different (P > 0.05) from those achieved with azithromycin. Similar results were also obtained in a lung infection model. Male C57BL/J6 mice inoculated intranasally with 10(6) inclusion-forming units of C. pneumoniae were treated with either PEX or azithromycin plus rifampin. Infected mice treated with PEX showed a marked decrease in C. pneumoniae counts versus those for the controls; this finding did not differ significantly (P > 0.05) from the results observed for the antibiotic-treated group. Integrin alpha(v)beta(3) plays an important role in C. pneumoniae infection. Blockage of integrin activation led to a significant inhibition of C. pneumoniae infection in HeLa cells. Moreover, CHO(DHFR) alpha(v)beta(3)-expressing cells were significantly (P < 0.001) more susceptible to C. pneumoniae infection than CHO(DHFR) cells. These results offer new perspectives on the treatment of C. pneumoniae infection and indicate that alpha(v)beta(3) could be a promising target for new agents developed for activity against this pathogen.
肺炎衣原体是一种与急慢性呼吸道感染相关的病原体，还与哮喘和冠状动脉疾病有关。在本研究中，我们评估了具有整合素结合活性的非催化金属蛋白酶片段PEX对肺炎衣原体引起的实验性感染的影响。此外，我们研究了肺炎衣原体与α(v)β(3)整合素功能之间的关系，以解释PEX在体外和体内可能的作用机制。对于体外实验，用肺炎衣原体感染HeLa细胞，并用PEX或阿奇霉素处理。PEX获得的结果与阿奇霉素获得的结果无显著差异（P>0.05）。在肺部感染模型中也获得了类似结果。用10(6)个肺炎衣原体包涵体形成单位经鼻接种的雄性C57BL/J6小鼠，用PEX或阿奇霉素加利福平处理。与对照组相比，用PEX处理的感染小鼠的肺炎衣原体数量显著减少；这一发现与抗生素治疗组观察到的结果无显著差异（P>0.05）。整合素α(v)β(3)在肺炎衣原体感染中起重要作用。整合素激活的阻断导致HeLa细胞中肺炎衣原体感染的显著抑制。此外，表达CHO(DHFR)α(v)β(3)的细胞比CHO(DHFR)细胞对肺炎衣原体感染的敏感性显著更高（P<0.001）。这些结果为肺炎衣原体感染的治疗提供了新的视角，并表明α(v)β(3)可能是开发针对该病原体活性的新型药物的有希望的靶点。
