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Role of nitric oxide synthases in elastase-induced emphysema.
Lab Invest. 2011 Mar; 91(3):353-62.LI

Abstract

Nitric oxide (NO) in combination with superoxide produces peroxynitrites and induces protein nitration, which participates in a number of chronic degenerative diseases. NO is produced at high levels in the human emphysematous lung, but its role in this disease is unknown. The aim of this study was to determine whether the NO synthases contribute to the development of elastase-induced emphysema in mice. nNOS, iNOS, and eNOS were quantified and immunolocalized in the lung after a tracheal instillation of elastase in mice. To determine whether eNOS or iNOS had a role in the development of emphysema, mice bearing a germline deletion of the eNOS and iNOS genes and mice treated with a pharmacological iNOS inhibitor were exposed to elastase. Protein nitration was determined by immunofluorescence, protein oxidation was determined by ELISA. Inflammation and MMP activity were quantified by cell counts, RT-PCR and zymography in bronchoalveolar lavage fluid. Cell proliferation was determined by Ki67 immunostaining. Emphysema was quantified morphometrically. iNOS and eNOS were diffusely upregulated in the lung of elastase-treated mice and a 12-fold increase in the number of 3-nitrotyrosine-expressing cells was observed. Over 80% of these cells were alveolar type 2 cells. In elastase-instilled mice, iNOS inactivation reduced protein nitration and increased protein oxidation but had no effect on inflammation, MMP activity, cell proliferation or the subsequent development of emphysema. eNOS inactivation had no effect. In conclusion, in the elastase-injured lung, iNOS mediates protein nitration in alveolar type 2 cells and alleviates oxidative injury. Neither eNOS nor iNOS are required for the development of elastase-induced emphysema.

Authors+Show Affiliations

INSERM, Unité U955, Créteil, France. laurent.boyer@hmn.aphp.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20956973

Citation

Boyer, Laurent, et al. "Role of Nitric Oxide Synthases in Elastase-induced Emphysema." Laboratory Investigation; a Journal of Technical Methods and Pathology, vol. 91, no. 3, 2011, pp. 353-62.
Boyer L, Plantier L, Dagouassat M, et al. Role of nitric oxide synthases in elastase-induced emphysema. Lab Invest. 2011;91(3):353-62.
Boyer, L., Plantier, L., Dagouassat, M., Lanone, S., Goven, D., Caramelle, P., Berrehar, F., Kerbrat, S., Dinh-Xuan, A. T., Crestani, B., Le Gouvello, S., & Boczkowski, J. (2011). Role of nitric oxide synthases in elastase-induced emphysema. Laboratory Investigation; a Journal of Technical Methods and Pathology, 91(3), 353-62. https://doi.org/10.1038/labinvest.2010.169
Boyer L, et al. Role of Nitric Oxide Synthases in Elastase-induced Emphysema. Lab Invest. 2011;91(3):353-62. PubMed PMID: 20956973.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of nitric oxide synthases in elastase-induced emphysema. AU - Boyer,Laurent, AU - Plantier,Laurent, AU - Dagouassat,Maylis, AU - Lanone,Sophie, AU - Goven,Delphine, AU - Caramelle,Philippe, AU - Berrehar,François, AU - Kerbrat,Stephane, AU - Dinh-Xuan,Anh-Tuan, AU - Crestani,Bruno, AU - Le Gouvello,Sabine, AU - Boczkowski,Jorge, Y1 - 2010/10/18/ PY - 2010/10/20/entrez PY - 2010/10/20/pubmed PY - 2011/4/20/medline SP - 353 EP - 62 JF - Laboratory investigation; a journal of technical methods and pathology JO - Lab Invest VL - 91 IS - 3 N2 - Nitric oxide (NO) in combination with superoxide produces peroxynitrites and induces protein nitration, which participates in a number of chronic degenerative diseases. NO is produced at high levels in the human emphysematous lung, but its role in this disease is unknown. The aim of this study was to determine whether the NO synthases contribute to the development of elastase-induced emphysema in mice. nNOS, iNOS, and eNOS were quantified and immunolocalized in the lung after a tracheal instillation of elastase in mice. To determine whether eNOS or iNOS had a role in the development of emphysema, mice bearing a germline deletion of the eNOS and iNOS genes and mice treated with a pharmacological iNOS inhibitor were exposed to elastase. Protein nitration was determined by immunofluorescence, protein oxidation was determined by ELISA. Inflammation and MMP activity were quantified by cell counts, RT-PCR and zymography in bronchoalveolar lavage fluid. Cell proliferation was determined by Ki67 immunostaining. Emphysema was quantified morphometrically. iNOS and eNOS were diffusely upregulated in the lung of elastase-treated mice and a 12-fold increase in the number of 3-nitrotyrosine-expressing cells was observed. Over 80% of these cells were alveolar type 2 cells. In elastase-instilled mice, iNOS inactivation reduced protein nitration and increased protein oxidation but had no effect on inflammation, MMP activity, cell proliferation or the subsequent development of emphysema. eNOS inactivation had no effect. In conclusion, in the elastase-injured lung, iNOS mediates protein nitration in alveolar type 2 cells and alleviates oxidative injury. Neither eNOS nor iNOS are required for the development of elastase-induced emphysema. SN - 1530-0307 UR - https://www.unboundmedicine.com/medline/citation/20956973/Role_of_nitric_oxide_synthases_in_elastase_induced_emphysema_ L2 - https://doi.org/10.1038/labinvest.2010.169 DB - PRIME DP - Unbound Medicine ER -