Role of Bone Marrow-Derived HPCs in Pulmonary Fibrosis

Interesting article from AJRCCM just published online that adds to accumulating data implicating circulating bone marrow-derived hematopoietic progenitor cells in the development of lung fibrosis.  Abstract below.

Rationale: Bone marrow (BM)-derived cells have been implicated in pulmonary fibrosis, however, their precise role in pathogenesis is incompletely understood.

Objectives: To elucidate roles of BM-derived cells in bleomycin induced pulmonary fibrosis, and clarify their potential relationship to lung hematopoietic progenitor cells (LHPCs).

Methods: GFP BM-chimera mice treated with or without bleomycin were used to assess the BM derived-cells.

Measurements and Main Results: GFP⁺ cells in the chimera lung were found to be comprised of two distinct phenotypes, namely GFP^hi and GFP^low cells. The GFP⁺, but not GFP^low, population was significantly increased after bleomycin treatment. Flow-cytometric analysis and quantitative RT-PCR revealed that GFP^hi cells exhibited phenotypic characteristics of CD11c⁺ dendritic cells/macrophages. GFP^hi cell conditioned media were chemotactic for fibroblasts obtained from fibrotic but not normal lung in vitro. Moreover, adoptive transfer of GFP^hi cells exacerbated fibrosis in recipient mice, similar to that seen upon adoptive transfer of BM-derived CD11c⁺ cells from donor bleomycin-treated mice. Next, we evaluated the potential of LHPCs as the source of GFP^hi cells. Isolation of LHPCs by flow sorting revealed enrichment in cKit⁺/Sca1^-/Lin^- cells, most of which were GFP⁺ indicating their BM origin. The number of LHPCs increased rapidly after bleomycin treatment. Furthermore, SCF induced LHPC proliferation, while GM-CSF induced differentiation to GFP^hi cells.

Conclusions: BM-derived LHPCs with a novel phenotype could differentiate into GFP^hi cells, which enhanced pulmonary fibrosis. Targeting this mobilized LHPCs might represent a novel therapeutic approach in chronic fibrotic lung diseases.


Read More: http://www.atsjournals.org/doi/abs/10.1164/rccm.201303-0479OC