Elevated endothelial progenitor cells may characterise PAH patients

By Eleanor McDermid

Plasma levels of endothelial progenitor cells (EPCs) are elevated in patients with pulmonary arterial hypertension (PAH), say researchers.

The team found that EPCs - identified from the cell surface markers CD34 and CD133 - accounted for an average of 0.6% of circulating lymphocytic cells in 20 PAH patients compared with 0.3% in 15 controls.

The proportion of CD34/CD133+ cells also positive for CD45 was also increased in PAH patients versus controls, at 66.7% versus 57.0%, indicating an increase in cells with a bone marrow origin. However, the cells did not carry markers of mature cells, such as the chemokine receptor CXCR2 or the macrophage/granulocyte marker CD16, indicating that these bone marrow-derived cells remained in an undifferentiated state.

The increase in bone marrow-derived cells may "indicate that the pulmonary vasculopathy, especially the elevated pulmonary pressure, is a driving force for the mobilisation of these cells from the bone marrow", say Horst Olschewski (Medical University of Graz, Austria) and study co-authors.

"Alternatively, it could indicate that the elevation of the total CD133+ population is pathogenic in PAH."

The CD133+ cells were heterogeneous, however, with some subpopulations increased and others reduced in PAH patients compared with controls. Levels of CD133+ cells also positive for CD117 were increased (31.4% vs 21.9%), whereas those positive for CD309, CD31 and CXCR2 were reduced.

Lymphocytes as a whole, however, were significantly decreased in the PAH patients, comprising 73.4% of cirulcating lymphomonocytic cells compared with 86.9% in controls.

"We can only speculate on the nature of the missing lymphocytes and it remains an open question if these cells are abundantly recruited in the tissue or if their production is reduced in PAH", write the researchers in the European Respiratory Journal.

In lung tissue samples from PAH patients, cells that stained positive for CD133 were mostly type 2 pneumocytes, located at the alveolar/septal junction. These cells "secrete surfactant and differentiate into type 1 pneumocytes following lung injury", explains the team.

Not all type 2 pneumocytes were positive for CD133, however, and there were also a few monocytic and undifferentiated cells that expressed the marker.

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