Document Detail

Evidence for cell fusion is absent in vascular lesions associated with pulmonary arterial hypertension.
MedLine Citation:
PMID:  18931051     Owner:  NLM     Status:  MEDLINE    
Pulmonary arterial hypertension (PAH) is a fatal disease associated with severe remodeling of the large and small pulmonary arteries. Increased accumulation of inflammatory cells and apoptosis-resistant cells are contributing factors. Proliferative apoptosis-resistant cells expressing CD133 are increased in the circulation of PAH patients. Circulating cells can contribute to tissue repair via cell fusion and heterokaryon formation. We therefore hypothesized that in the presence of increased leukocytes and CD133-positive (CD133(pos)) cells in PAH lung tissue, cell fusion and resulting genomic instability could account for abnormal cell proliferation and the genesis of vascular lesions. We performed analyses of CD45/CD133 localization, cell fusion, and proliferation during late-stage PAH in human lung tissue from control subjects and subjects with idiopathic (IPAH) and familial (FPAH) PAH. Localization, proliferation, and quantitation of cell populations in individual patients were performed by immunolocalization. The occurrence of cellular fusion in vascular lesions was analyzed in lung tissue by fluorescence in situ hybridization. We found the accumulation of CD45(pos) leukocytic cells in the tissue parenchyma and perivascular regions in PAH patients and less frequently observed myeloid cells (CD45/CD11b). CD133(pos) cells were detected in occlusive lesions and perivascular areas in those with PAH and were more numerous in those with IPAH lesions than in FPAH lesions. Cells coexpressing CD133 and smooth muscle alpha-actin were occasionally observed in occlusive lesions and perivascular areas. Proliferating cells were more prominent in IPAH lesions and colocalized with CD45 or CD133. We found no evidence of increased ploidy to suggest cell fusion. Taken together, these data suggest that abnormal lesion formation in PAH occurs in the absence of cell fusion.
S M Majka; M Skokan; L Wheeler; J Harral; S Gladson; E Burnham; J E Loyd; K R Stenmark; M Varella-Garcia; J West
Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-10-17
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  295     ISSN:  1040-0605     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-02     Completed Date:  2009-01-22     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L1028-39     Citation Subset:  IM    
Cardiovascular Pulmonary Research, University of Colorado Denver, Aurora, Colorado 80045, USA.
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MeSH Terms
Antigens, CD / metabolism
Antigens, CD45 / biosynthesis
Cell Fusion
Cell Proliferation
Giant Cells / metabolism,  pathology
Glycoproteins / metabolism
Hypertension, Pulmonary / metabolism,  pathology*
Lung / metabolism,  pathology*
Middle Aged
Myeloid Cells / metabolism,  pathology*
Peptides / metabolism
Pulmonary Artery / metabolism,  pathology*
Grant Support
HL-82694/HL/NHLBI NIH HHS; P01 072058//PHS HHS; R01 HL082694/HL/NHLBI NIH HHS
Reg. No./Substance:
0/AC133 antigen; 0/Antigens, CD; 0/Glycoproteins; 0/Peptides; EC, CD45; EC protein, human

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