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...

Ausführliche Beschreibung

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 104(2002), 2 vom: 01. Aug., Seite 191-8
1. Verfasser: Raychaudhuri, Baisakhi (VerfasserIn)
Weitere Verfasser: Bonfield, Tracey L, Malur, Anagha, Hague, Kathleen, Kavuru, Mani S, Arroliga, Alejandro C, Thomassen, Mary Jane
Format: Aufsatz
Sprache:English
Veröffentlicht: 2002
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... Macrophage Inflammatory Proteins Membrane Glycoproteins NF-kappa B RNA, Messenger Receptors, Cell Surface TLR2 protein, human TLR4 protein, human Toll-Like Receptor 2 Toll-Like Receptor 4 Toll-Like Receptors
LEADER 01000naa a22002652 4500
001 NLM120261197
003 DE-627
005 20231222190516.0
007 tu
008 231222s2002 xx ||||| 00| ||eng c
028 5 2 |a pubmed24n0401.xml 
035 |a (DE-627)NLM120261197 
035 |a (NLM)12165280 
040 |a DE-627  |b ger  |c DE-627  |e rakwb 
041 |a eng 
100 1 |a Raychaudhuri, Baisakhi  |e verfasserin  |4 aut 
245 1 0 |a Circulating monocytes from patients with primary pulmonary hypertension are hyporesponsive 
264 1 |c 2002 
336 |a Text  |b txt  |2 rdacontent 
337 |a ohne Hilfsmittel zu benutzen  |b n  |2 rdamedia 
338 |a Band  |b nc  |2 rdacarrier 
500 |a Date Completed 10.10.2002 
500 |a Date Revised 06.11.2019 
500 |a published: Print 
500 |a Citation Status MEDLINE 
520 |a 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 
650 4 |a Comparative Study 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 7 |a Chemokine CCL3  |2 NLM 
650 7 |a Chemokine CCL4  |2 NLM 
650 7 |a Cytokines  |2 NLM 
650 7 |a Drosophila Proteins  |2 NLM 
650 7 |a HLA-DR Antigens  |2 NLM 
650 7 |a Lipopolysaccharide Receptors  |2 NLM 
650 7 |a Lipopolysaccharides  |2 NLM 
650 7 |a Macrophage Inflammatory Proteins  |2 NLM 
650 7 |a Membrane Glycoproteins  |2 NLM 
650 7 |a NF-kappa B  |2 NLM 
650 7 |a RNA, Messenger  |2 NLM 
650 7 |a Receptors, Cell Surface  |2 NLM 
650 7 |a TLR2 protein, human  |2 NLM 
650 7 |a TLR4 protein, human  |2 NLM 
650 7 |a Toll-Like Receptor 2  |2 NLM 
650 7 |a Toll-Like Receptor 4  |2 NLM 
650 7 |a Toll-Like Receptors  |2 NLM 
700 1 |a Bonfield, Tracey L  |e verfasserin  |4 aut 
700 1 |a Malur, Anagha  |e verfasserin  |4 aut 
700 1 |a Hague, Kathleen  |e verfasserin  |4 aut 
700 1 |a Kavuru, Mani S  |e verfasserin  |4 aut 
700 1 |a Arroliga, Alejandro C  |e verfasserin  |4 aut 
700 1 |a Thomassen, Mary Jane  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Clinical immunology (Orlando, Fla.)  |d 1999  |g 104(2002), 2 vom: 01. Aug., Seite 191-8  |w (DE-627)NLM098196855  |x 1521-7035  |7 nnns 
773 1 8 |g volume:104  |g year:2002  |g number:2  |g day:01  |g month:08  |g pages:191-8 
912 |a GBV_USEFLAG_A 
912 |a SYSFLAG_A 
912 |a GBV_NLM 
912 |a GBV_ILN_11 
912 |a GBV_ILN_24 
912 |a GBV_ILN_350 
951 |a AR 
952 |d 104  |j 2002  |e 2  |b 01  |c 08  |h 191-8