Bone Marrow-derived Cells Contribute to the Pathogenesis of Pulmonary Arterial Hypertension.
Am J Respir Crit Care Med
; 193(8): 898-909, 2016 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-26651104
ABSTRACT
RATIONALE Pulmonary arterial hypertension (PAH) is a progressive lung disease of the pulmonary microvasculature. Studies suggest that bone marrow (BM)-derived circulating cells may play an important role in its pathogenesis. OBJECTIVES:
We used a genetic model of PAH, the Bmpr2 mutant mouse, to study the role of BM-derived circulating cells in its pathogenesis.METHODS:
Recipient mice, either Bmpr2(R899X) mutant or controls, were lethally irradiated and transplanted with either control or Bmpr2(R899X) BM cells. Donor cells were traced in female recipient mice by Y chromosome painting. Molecular and function insights were provided by expression and cytokine arrays combined with flow cytometry, colony-forming assays, and competitive transplant assays. MEASUREMENTS AND MAINRESULTS:
We found that mutant BM cells caused PAH with remodeling and inflammation when transplanted into control mice, whereas control BM cells had a protective effect against the development of disease, when transplanted into mutant mice. Donor BM-derived cells were present in the lungs of recipient mice. Functional and molecular analysis identified mutant BM cell dysfunction suggestive of a PAH phenotype soon after activation of the transgene and long before the development of lung pathology.CONCLUSIONS:
Our data show that BM cells played a key role in PAH pathogenesis and that the transplanted BM cells were able to drive the lung phenotype in a myeloablative transplant model. Furthermore, the specific cell types involved were derived from hematopoietic stem cells and exhibit dysfunction long before the development of lung pathology.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Transplante de Medula Óssea
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Hipertensão Pulmonar
/
Pulmão
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Am J Respir Crit Care Med
Ano de publicação:
2016
Tipo de documento:
Article