CD133+ cells in pulmonary arterial hypertension.
Circulating mononuclear cells may play an important role for the vascular remodelling in pulmonary arterial hypertension (PAH), but studies addressing multiple progenitor populations are rare and inconsistent.We used a comprehensive fluorescence-activated cell sorting analysis of circulating mononuclear cells in 20 PAH patients and 20 age- and sex-matched controls, and additionally analysed CD133(+) cells in the lung tissue of five PAH transplant recipients and five healthy controls (donor lungs).PAH patients were characterised by increased numbers of circulating CD133(+) cells and lymphopenia as compared with control. In PAH, CD133(+) subpopulations positive for CD117 or CD45 were significantly increased, whereas CD133(+)CD309(+), CD133(+)CXCR2(+) and CD133(+)CD31(+) cells were decreased. In CD133(+) cells, SOX2, Nanog, Ki67 and CXCR4 were not detected, but Oct3/4 mRNA was present in both PAH and controls. In the lung tissue, CD133(+) cells included three main populations: type 2 pneumocytes, monocytes and undifferentiated cells without significant differences between PAH and controls.In conclusion, circulating CD133(+) progenitor cells are elevated in PAH and consist of phenotypically different subpopulations that may be up- or downregulated. This may explain the inconsistent results in the literature. CD133(+) type 2 pneumocytes in the lung tissue are not associated with circulating CD133(+) mononuclear cells.
Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria Dept of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria.
Vasile
V
Foris
Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria Dept of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria.
Gabor
G
Kovacs
Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
Leigh M
LM
Marsh
Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
Zoltán
Z
Bálint
Institute of Cytology, Medical University of Graz, Graz, Austria.
Martin
M
Tötsch
Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
Alexander
A
Avian
Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria Dept of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria.
Philipp
P
Douschan
Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
Bahil
B
Ghanim
Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
Walter
W
Klepetko
Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria Dept of Anaesthesia and Intensive Care, Experimental Anaesthesiology, Medical University of Graz, Graz, Austria.
Andrea
A
Olschewski
Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria Dept of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria horst.olschewski@medunigraz.at.
Horst
H
Olschewski
D000071916:AC133 Antigen / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011651:Pulmonary Artery / Q000473:pathology; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013234:Stem Cells; D066253:Vascular Remodeling; D055815:Young Adult
D000071916:AC133 Antigen; C000606023:PROM1 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D023063:Receptors, Interleukin-8B; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D019009:Proto-Oncogene Proteins c-kit; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human