RATIONALE: @entity120 ( @entity120 ) is a progressive @entity358 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 @entity120 , the @entity34544 mutant @entity19 , to study the role of BM-derived circulating cells in its pathogenesis. METHODS: Recipient @entity19 , either @entity34544 ( @entity34545 ) mutant or controls, were lethally irradiated and transplanted with either control or @entity34544 ( @entity34545 ) BM cells. Donor cells were traced in female recipient @entity19 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 MAIN RESULTS: We found that mutant BM cells caused @entity120 with @entity5707 and @entity32 when transplanted into control @entity19 , whereas control BM cells had a protective effect against the development of disease, when transplanted into mutant @entity19 . Donor BM-derived cells were present in the lungs of recipient @entity19 . Functional and molecular analysis identified mutant BM cell dysfunction suggestive of a @entity120 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 @entity120 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.

Bone Marrow-derived Cells Contribute to the Pathogenesis of XXXX .

@entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity120 :: ('MESH:D006976', 'Disease') :: ['PAH', 'Pulmonary arterial hypertension'] @entity34545 :: ('p|SUB|R|899|X', 'ProteinMutation') :: ['R899X'] @entity358 :: ('MESH:D008171', 'Disease') :: ['lung disease'] @entity5707 :: ('MESH:D020257', 'Disease') :: ['remodeling'] @entity34544 :: ('12168(Tax:10090)', 'Gene') :: ['Bmpr2']
@entity120 :: (MESH:D006976,Disease) :: ['Pulmonary Arterial Hypertension']
