Modification of hemodynamic and immune responses to exposure with a weak antigen by the expression of a hypomorphic BMPR2 gene.
Hypomorphic mutations in the bone morphogenic protein receptor (BMPR2) confer a much greater risk for developing pulmonary arterial hypertension (PAH). However, not all carriers of a mutation in the BMPR2 gene suffer from PAH. We have previously shown that prolonged T helper 2 (Th2) responses in the...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3558423?pdf=render |
| _version_ | 1828405464375754752 |
|---|---|
| author | Sung-Hyun Park Wen-Chi Chen Carol Hoffman Leigh M Marsh James West Gabriele Grunig |
| author_facet | Sung-Hyun Park Wen-Chi Chen Carol Hoffman Leigh M Marsh James West Gabriele Grunig |
| author_sort | Sung-Hyun Park |
| collection | DOAJ |
| description | Hypomorphic mutations in the bone morphogenic protein receptor (BMPR2) confer a much greater risk for developing pulmonary arterial hypertension (PAH). However, not all carriers of a mutation in the BMPR2 gene suffer from PAH. We have previously shown that prolonged T helper 2 (Th2) responses in the lungs to a mild antigen delivered via the airways induce severe pulmonary arterial remodeling, but no pulmonary hypertension. The current studies were designed to test the idea that Th2 responses to a mild antigen together with the expression of a hypomorphic BMPR2 gene would trigger pulmonary hypertension.Mice that expressed a hypomorphic BMPR2 transgene (transgene-positive) and transgene-negative mice were either exposed to saline, or primed and exposed to a mild antigen (Ovalbumin) over a prolonged period of time. Only transgene-positive but not transgene-negative mice exposed to antigen developed significantly increased right ventricular systolic pressures, while both groups showed pulmonary artery remodeling with severe muscularization and airway inflammation to a similar degree. Antigen exposure resulted in a smaller increase in the percentage of Interleukin (IL)-13 positive T cells in the lymph nodes, and in a smaller increase in resistin-like-molecule (RELM)α expression and a decreased ratio of expression of IL-33 relative to its receptor (IL-1-receptor-like 1, IL1RL1-ST2) in the right ventricles of transgene-positive mice compared to transgene-negative animals. Furthermore, only antigen-challenged transgene-positive mice showed a significant increase in Interferon (IFN)γ positive T cells over saline-exposed controls.Our study suggests that exposure with a mild Th2 antigen can trigger pulmonary hypertension on the background of the expression of a hypomorphic BMPR2 gene and that conversely, the expression of the hypomorphic BMPR2 gene can alter the immune response to a mild, inhaled antigen. |
| first_indexed | 2024-12-10T10:54:47Z |
| format | Article |
| id | doaj.art-791d6e3712bb4f769bd2d002eba47446 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T10:54:47Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-791d6e3712bb4f769bd2d002eba474462022-12-22T01:51:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5518010.1371/journal.pone.0055180Modification of hemodynamic and immune responses to exposure with a weak antigen by the expression of a hypomorphic BMPR2 gene.Sung-Hyun ParkWen-Chi ChenCarol HoffmanLeigh M MarshJames WestGabriele GrunigHypomorphic mutations in the bone morphogenic protein receptor (BMPR2) confer a much greater risk for developing pulmonary arterial hypertension (PAH). However, not all carriers of a mutation in the BMPR2 gene suffer from PAH. We have previously shown that prolonged T helper 2 (Th2) responses in the lungs to a mild antigen delivered via the airways induce severe pulmonary arterial remodeling, but no pulmonary hypertension. The current studies were designed to test the idea that Th2 responses to a mild antigen together with the expression of a hypomorphic BMPR2 gene would trigger pulmonary hypertension.Mice that expressed a hypomorphic BMPR2 transgene (transgene-positive) and transgene-negative mice were either exposed to saline, or primed and exposed to a mild antigen (Ovalbumin) over a prolonged period of time. Only transgene-positive but not transgene-negative mice exposed to antigen developed significantly increased right ventricular systolic pressures, while both groups showed pulmonary artery remodeling with severe muscularization and airway inflammation to a similar degree. Antigen exposure resulted in a smaller increase in the percentage of Interleukin (IL)-13 positive T cells in the lymph nodes, and in a smaller increase in resistin-like-molecule (RELM)α expression and a decreased ratio of expression of IL-33 relative to its receptor (IL-1-receptor-like 1, IL1RL1-ST2) in the right ventricles of transgene-positive mice compared to transgene-negative animals. Furthermore, only antigen-challenged transgene-positive mice showed a significant increase in Interferon (IFN)γ positive T cells over saline-exposed controls.Our study suggests that exposure with a mild Th2 antigen can trigger pulmonary hypertension on the background of the expression of a hypomorphic BMPR2 gene and that conversely, the expression of the hypomorphic BMPR2 gene can alter the immune response to a mild, inhaled antigen.http://europepmc.org/articles/PMC3558423?pdf=render |
| spellingShingle | Sung-Hyun Park Wen-Chi Chen Carol Hoffman Leigh M Marsh James West Gabriele Grunig Modification of hemodynamic and immune responses to exposure with a weak antigen by the expression of a hypomorphic BMPR2 gene. PLoS ONE |
| title | Modification of hemodynamic and immune responses to exposure with a weak antigen by the expression of a hypomorphic BMPR2 gene. |
| title_full | Modification of hemodynamic and immune responses to exposure with a weak antigen by the expression of a hypomorphic BMPR2 gene. |
| title_fullStr | Modification of hemodynamic and immune responses to exposure with a weak antigen by the expression of a hypomorphic BMPR2 gene. |
| title_full_unstemmed | Modification of hemodynamic and immune responses to exposure with a weak antigen by the expression of a hypomorphic BMPR2 gene. |
| title_short | Modification of hemodynamic and immune responses to exposure with a weak antigen by the expression of a hypomorphic BMPR2 gene. |
| title_sort | modification of hemodynamic and immune responses to exposure with a weak antigen by the expression of a hypomorphic bmpr2 gene |
| url | http://europepmc.org/articles/PMC3558423?pdf=render |
| work_keys_str_mv | AT sunghyunpark modificationofhemodynamicandimmuneresponsestoexposurewithaweakantigenbytheexpressionofahypomorphicbmpr2gene AT wenchichen modificationofhemodynamicandimmuneresponsestoexposurewithaweakantigenbytheexpressionofahypomorphicbmpr2gene AT carolhoffman modificationofhemodynamicandimmuneresponsestoexposurewithaweakantigenbytheexpressionofahypomorphicbmpr2gene AT leighmmarsh modificationofhemodynamicandimmuneresponsestoexposurewithaweakantigenbytheexpressionofahypomorphicbmpr2gene AT jameswest modificationofhemodynamicandimmuneresponsestoexposurewithaweakantigenbytheexpressionofahypomorphicbmpr2gene AT gabrielegrunig modificationofhemodynamicandimmuneresponsestoexposurewithaweakantigenbytheexpressionofahypomorphicbmpr2gene |