RT Journal Article
SR Electronic
T1 Roles of circulating and resident myeloid cell subpopulations in bronchopulmonary remodeling and pulmonary hypertension
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P5158
VO 42
IS Suppl 57
A1 Kelley Colvin
A1 Kurt Stenmark
A1 Michael Yeager
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P5158.abstract
AB Rationale: Pulmonary hypertension (PH) is characterized by vascular remodeling and the presence of myeloid cells. A clearer understanding of the myeloid cell phenotypes contributing to pulmonary vascular remodeling seems a pre-requisite for anti-inflammatory therapy for patients with PH.Methods: We used immunohistology, qPCR, cell sorting, and immunoblot on lung tissue and peripheral blood derived from rat (green fluorescent protein [GFP] bone marrow transplanted) PH models and humans with PH.Results: In human blood, we found increased fibrocytes in PH vs. controls, assessed as CD45+/procollagen+ (PH 1.2% of total white blood cells, WBC vs. controls 0.45% WBC) or vimentin+ (PH 1.9% vs. controls 1.35% WBC) or smooth muscle actin+ (PH 2.2% vs. controls 0.3% WBC) or heat shock protein 47+ (PH 0.27% vs. controls 0.078% WBC). No differences in myeloid derived suppressor cell (CD45+/CD33+/CD11b+/MHCII-) numbers were observed. PH patients expressed Fc gamma receptors (FcgR) CD16, CD32, and CD64 more robustly vs. controls. We found positive correlation between fibrocytes and cardiac output, and strong positive correlation between fibrocytes and expression of CD16 and CD32 FcgRs. Similar results were obtained using blood from rats with PH. FACS analysis of PH rat lungs confirmed increases in fibrocytes, as well as cells positive for CD68+, or CD163, or CD11c, CD103, CD206, and CD11b. Only CD11b cells were co-positive for GFP, a result confirmed by immunofluorescence of tissue sections.Conclusion: A clearer understanding of how myeloid cells impact the pathobiology of PH may have profound therapeutic significance.