Circulating monocytes from patients with primary pulmonary hypertension are hyporesponsive
Primary pulmonary hypertension (PPH) is a rare disease of unknown etiology characterized by arterial thickening and remodeling. The transcription factor NF-kappaB is responsible for the activation of several cytokines and growth factor genes reported to be associated with PPH. Our previous study sho...
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 104(2002), 2 vom: 01. Aug., Seite 191-8 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , |
| Format: | Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2002
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Comparative Study Journal Article Research Support, Non-U.S. Gov't Chemokine CCL3 Chemokine CCL4 Cytokines Drosophila Proteins HLA-DR Antigens Lipopolysaccharide Receptors Lipopolysaccharides mehr... |
| Zusammenfassung: | Primary pulmonary hypertension (PPH) is a rare disease of unknown etiology characterized by arterial thickening and remodeling. The transcription factor NF-kappaB is responsible for the activation of several cytokines and growth factor genes reported to be associated with PPH. Our previous study showed NF-kappaB activation in alveolar macrophages from PPH patients, suggesting the presence of a localized pulmonary inflammatory response. In PPH, circulating monocyte activity has not been previously examined. The present study was undertaken to determine whether circulating monocytes also showed evidence of activation, which could suggest a systemic response to PPH injury. Results indicated that NF-kappaB activation in monocytes from PPH patients did not differ from that of healthy controls. However, mRNA expression was decreased compared to controls for NF-kappaB-regulated genes, granulocyte macrophage colony-stimulating factor, interleukin-6, macrophage inflammatory protein-1alpha (MIP-1alpha), and vascular endothelial growth factor. MIP-1alpha protein secretion from PPH monocytes was also lower than that of controls cultured with and without endotoxin. Expression of the surface activation markers HLA-DR and CD-14 were significantly reduced on monocytes from PPH patients compared to healthy controls. Toll-like receptor-4 (TLR-4) expression was significantly increased on monocytes from PPH patients while TLR-2 remained unchanged. Thus, our data are the first to show that monocytes in PPH have decreased activation and are hyporesponsive to lipopolysaccharide (LPS) stimulation. The monocyte LPS hyporesponsiveness may in part be the result of decreased CD-14 expression, since LPS responsiveness is dependent on the physical association of LPS/CD-14 complexes with TLR-4, and without this association signal transduction does not occur. These data indicate that although PPH is a localized pulmonary disorder, there are alterations in the systemic compartment. What remains unknown is how the reduced activation of monocytes in PPH is related to the pulmonary vascular lesion |
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| Beschreibung: | Date Completed 10.10.2002 Date Revised 06.11.2019 published: Print Citation Status MEDLINE |
| ISSN: | 1521-7035 |