Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Park, SH; Chen, WC; Hoffman, C; Marsh, LM; West, J; Grunig, G.
Modification of hemodynamic and immune responses to exposure with a weak antigen by the expression of a hypomorphic BMPR2 gene.
PLoS One. 2013; 8(1): e55180-e55180.
Doi: 10.1371/journal.pone.0055180
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- Co-Autor*innen der Med Uni Graz
- Marsh Leigh
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- Abstract:
- Background: 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. Methodology/Principal Findings: 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)alpha 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)gamma positive T cells over saline-exposed controls. Conclusions/Significance: 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antigens - administration & dosage Antigens - immunology
- Blood Pressure - physiology
- Body Weight - physiology
- Bone Morphogenetic Protein Receptors, Type II - genetics Bone Morphogenetic Protein Receptors, Type II - metabolism
- Bronchoalveolar Lavage -
- DNA Primers - genetics
- Heart Ventricles - pathology
- Hemodynamics -
- Hypertension, Pulmonary - etiology Hypertension, Pulmonary - immunology Hypertension, Pulmonary - metabolism
- Intercellular Signaling Peptides and Proteins - metabolism
- Interleukins - metabolism
- Mice -
- Mice, Transgenic -
- Organ Size - physiology
- Ovalbumin - administration & dosage Ovalbumin - immunology
- Receptors, Interleukin - metabolism
- Th2 Cells - immunology
- Transgenes - genetics