Impact of immunization against OxLDL on the pulmonary response to cigarette smoke exposure in mice
Abstract Background Cigarette smoke exposure can affect pulmonary lipid homeostasis and cause a progressive increase in pulmonary antibodies against oxidized low-density lipoproteins (OxLDL). Similarly, increased anti-OxLDL antibodies are observed in atherosclerosis, a pathology also tightly associa...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-07-01
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| Series: | Respiratory Research |
| Online Access: | http://link.springer.com/article/10.1186/s12931-018-0833-9 |
| _version_ | 1818060154411679744 |
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| author | Maude Talbot Mélanie Hamel-Auger Marie-Josée Beaulieu Morgan Gazzola Ariane Lechasseur Sophie Aubin Marie-Ève Paré David Marsolais Ynuk Bossé Mathieu C. Morissette |
| author_facet | Maude Talbot Mélanie Hamel-Auger Marie-Josée Beaulieu Morgan Gazzola Ariane Lechasseur Sophie Aubin Marie-Ève Paré David Marsolais Ynuk Bossé Mathieu C. Morissette |
| author_sort | Maude Talbot |
| collection | DOAJ |
| description | Abstract Background Cigarette smoke exposure can affect pulmonary lipid homeostasis and cause a progressive increase in pulmonary antibodies against oxidized low-density lipoproteins (OxLDL). Similarly, increased anti-OxLDL antibodies are observed in atherosclerosis, a pathology also tightly associated with smoking and lipid homeostasis disruption. Several immunization strategies against oxidized lipid species to help with their clearance have been shown to reduce the formation of atherosclerotic lesions. Since oxidized lipids are generated during cigarette smoke exposure, we investigated the impact of a prophylactic immunization protocol against OxLDL on the pulmonary effects of cigarette smoke exposure in mice. Methods Mice were immunized systemically with a mixture of human OxLDL (antigen source) and AddaVax (adjuvant) or PBS alone prior to the initiation of acute (2 week) or sub-chronic (8 weeks) cigarette smoke exposure protocols. Anti-OxLDL antibodies were measured in the bronchoalveolar lavage (BAL) fluid and serum by direct ELISA. Pulmonary impacts of cigarette smoke exposure and OxLDL immunization were assessed by measuring BAL inflammatory cells, lung functions, and changes in lung structure and gene levels of matrix/matrix-related genes. Results Immunization to OxLDL led to a marked increase in circulating and pulmonary antibodies against OxLDL that persisted during cigarette smoke exposure. OxLDL immunization did not exacerbate or reduce the inflammatory response following acute or sub-chronic exposure to cigarette smoke. OxLDL immunization alone had effects similar to cigarette smoke exposure on lung functions but OxLDL immunization and cigarette smoke exposure had no additive effects on these parameters. No obvious changes in lung histology, airspace or levels of matrix and matrix-related genes were caused by OxLDL immunization compared to vehicle treatment. Conclusions Overall, this study shows for the first time that a prophylactic immunization protocol against OxLDL can potentially have detrimental effects lung functions, without having additive effects over cigarette smoke exposure. This work sheds light on a complex dynamic between anti-OxLDL antibodies and the pulmonary response to cigarette smoke exposure. |
| first_indexed | 2024-12-10T13:27:54Z |
| format | Article |
| id | doaj.art-aa0b5766e35247b488cc0a8791e74293 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-12-10T13:27:54Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-aa0b5766e35247b488cc0a8791e742932022-12-22T01:47:06ZengBMCRespiratory Research1465-993X2018-07-011911910.1186/s12931-018-0833-9Impact of immunization against OxLDL on the pulmonary response to cigarette smoke exposure in miceMaude Talbot0Mélanie Hamel-Auger1Marie-Josée Beaulieu2Morgan Gazzola3Ariane Lechasseur4Sophie Aubin5Marie-Ève Paré6David Marsolais7Ynuk Bossé8Mathieu C. Morissette9Faculty of Medicine, Université LavalFaculty of Medicine, Université LavalQuebec Heart and Lung Institute - Université LavalFaculty of Medicine, Université LavalFaculty of Medicine, Université LavalQuebec Heart and Lung Institute - Université LavalQuebec Heart and Lung Institute - Université LavalQuebec Heart and Lung Institute - Université LavalQuebec Heart and Lung Institute - Université LavalQuebec Heart and Lung Institute - Université LavalAbstract Background Cigarette smoke exposure can affect pulmonary lipid homeostasis and cause a progressive increase in pulmonary antibodies against oxidized low-density lipoproteins (OxLDL). Similarly, increased anti-OxLDL antibodies are observed in atherosclerosis, a pathology also tightly associated with smoking and lipid homeostasis disruption. Several immunization strategies against oxidized lipid species to help with their clearance have been shown to reduce the formation of atherosclerotic lesions. Since oxidized lipids are generated during cigarette smoke exposure, we investigated the impact of a prophylactic immunization protocol against OxLDL on the pulmonary effects of cigarette smoke exposure in mice. Methods Mice were immunized systemically with a mixture of human OxLDL (antigen source) and AddaVax (adjuvant) or PBS alone prior to the initiation of acute (2 week) or sub-chronic (8 weeks) cigarette smoke exposure protocols. Anti-OxLDL antibodies were measured in the bronchoalveolar lavage (BAL) fluid and serum by direct ELISA. Pulmonary impacts of cigarette smoke exposure and OxLDL immunization were assessed by measuring BAL inflammatory cells, lung functions, and changes in lung structure and gene levels of matrix/matrix-related genes. Results Immunization to OxLDL led to a marked increase in circulating and pulmonary antibodies against OxLDL that persisted during cigarette smoke exposure. OxLDL immunization did not exacerbate or reduce the inflammatory response following acute or sub-chronic exposure to cigarette smoke. OxLDL immunization alone had effects similar to cigarette smoke exposure on lung functions but OxLDL immunization and cigarette smoke exposure had no additive effects on these parameters. No obvious changes in lung histology, airspace or levels of matrix and matrix-related genes were caused by OxLDL immunization compared to vehicle treatment. Conclusions Overall, this study shows for the first time that a prophylactic immunization protocol against OxLDL can potentially have detrimental effects lung functions, without having additive effects over cigarette smoke exposure. This work sheds light on a complex dynamic between anti-OxLDL antibodies and the pulmonary response to cigarette smoke exposure.http://link.springer.com/article/10.1186/s12931-018-0833-9 |
| spellingShingle | Maude Talbot Mélanie Hamel-Auger Marie-Josée Beaulieu Morgan Gazzola Ariane Lechasseur Sophie Aubin Marie-Ève Paré David Marsolais Ynuk Bossé Mathieu C. Morissette Impact of immunization against OxLDL on the pulmonary response to cigarette smoke exposure in mice Respiratory Research |
| title | Impact of immunization against OxLDL on the pulmonary response to cigarette smoke exposure in mice |
| title_full | Impact of immunization against OxLDL on the pulmonary response to cigarette smoke exposure in mice |
| title_fullStr | Impact of immunization against OxLDL on the pulmonary response to cigarette smoke exposure in mice |
| title_full_unstemmed | Impact of immunization against OxLDL on the pulmonary response to cigarette smoke exposure in mice |
| title_short | Impact of immunization against OxLDL on the pulmonary response to cigarette smoke exposure in mice |
| title_sort | impact of immunization against oxldl on the pulmonary response to cigarette smoke exposure in mice |
| url | http://link.springer.com/article/10.1186/s12931-018-0833-9 |
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