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Antimicrobial Agents and Chemotherapy, October 2006, p. 3277-3282, Vol. 50, No. 10
0066-4804/06/$08.00+0     doi:10.1128/AAC.00108-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Effect of PEX, a Noncatalytic Metalloproteinase Fragment with Integrin-Binding Activity, on Experimental Chlamydophila pneumoniae Infection

Dario Caronzolo,¹ Valeria Lucini,¹ Marilou Pannacci,¹ Silvia Grosso,¹ Nelly Kieffer,² Lorenzo Bello,³ Andreas Bikfalvi,⁴ and Francesco Scaglione^1*

Department of Pharmacology, Chemotherapy, and Toxicology, University of Milan, Milan, Italy,¹ Laboratoire de Biologie et Physiologie Intégrée (CNRS/GDRE-ITI), Université du Luxembourg, Grand-Duché du Luxembourg,² Neurosurgery, Department of Neurological Sciences, University of Milan, and Ospedale Maggiore Policlinico, IRCCS, Milan, Italy,³ INSERM Unit 0113, Molecular Mechanisms of Angiogenesis, University of Bordeaux 1, Talence, France⁴

Received 26 January 2006/ Returned for modification 27 January 2006/ Accepted 7 July 2006

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 _vß₃ 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 10⁶ 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 _vß₃ 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 v}ß₃-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 _vß₃ could be a promising target for new agents developed for activity against this pathogen.

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* Corresponding author. Mailing address: Department of Pharmacology, Chemotherapy, and Toxicology, University of Milan, Via Vanvitelli No. 32, 20129 Milan, Italy. Phone: 39 0250317049. Fax: 39 0250317050. E-mail: francesco.scaglione{at}unimi.it.

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Antimicrobial Agents and Chemotherapy, October 2006, p. 3277-3282, Vol. 50, No. 10
0066-4804/06/$08.00+0     doi:10.1128/AAC.00108-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.