Evidence for cell fusion is absent in vascular lesions associated with pulmonary arterial hypertension
| Autor: | James West, Marileila Varella-Garcia, Susan M. Majka, M. Skokan, Kurt R. Stenmark, Ellen L. Burnham, Julie W. Harral, James E. Loyd, Lisa Wheeler, Santhi Gladson |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Physiology Hypertension Pulmonary Cell Apoptosis Pulmonary Artery Biology Giant Cells Cell Fusion Lesion Antigens CD Physiology (medical) Parenchyma medicine Humans Myeloid Cells AC133 Antigen Child Lung Cell Proliferation Glycoproteins Cell fusion Cell growth Articles Cell Biology Middle Aged medicine.disease Pulmonary hypertension medicine.anatomical_structure Giant cell Leukocyte Common Antigens Female medicine.symptom Peptides |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 295:L1028-L1039 |
| ISSN: | 1522-1504 1040-0605 |
| Popis: | 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 (CD133pos) 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 CD45pos leukocytic cells in the tissue parenchyma and perivascular regions in PAH patients and less frequently observed myeloid cells (CD45/CD11b). CD133pos 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 α-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. |
| Databáze: | OpenAIRE |
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