PMID- 12165280
OWN - NLM
STAT- MEDLINE
DCOM- 20021010
LR  - 20191106
IS  - 1521-6616 (Print)
IS  - 1521-6616 (Linking)
VI  - 104
IP  - 2
DP  - 2002 Aug
TI  - Circulating monocytes from patients with primary pulmonary hypertension are 
      hyporesponsive.
PG  - 191-8
AB  - 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.
FAU - Raychaudhuri, Baisakhi
AU  - Raychaudhuri B
AD  - Department of Pulmonary and Critical Care Medicine, The Cleveland Clinic 
      Foundation, Cleveland, OH 44195, USA.
FAU - Bonfield, Tracey L
AU  - Bonfield TL
FAU - Malur, Anagha
AU  - Malur A
FAU - Hague, Kathleen
AU  - Hague K
FAU - Kavuru, Mani S
AU  - Kavuru MS
FAU - Arroliga, Alejandro C
AU  - Arroliga AC
FAU - Thomassen, Mary Jane
AU  - Thomassen MJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Immunol
JT  - Clinical immunology (Orlando, Fla.)
JID - 100883537
RN  - 0 (Chemokine CCL3)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Cytokines)
RN  - 0 (Drosophila Proteins)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (TLR2 protein, human)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Chemokine CCL3
MH  - Chemokine CCL4
MH  - Cytokines/analysis
MH  - *Drosophila Proteins
MH  - Female
MH  - HLA-DR Antigens/biosynthesis
MH  - Humans
MH  - Hypertension, Pulmonary/blood/*immunology
MH  - Lipopolysaccharide Receptors/biosynthesis
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophage Inflammatory Proteins/analysis
MH  - Male
MH  - Membrane Glycoproteins/biosynthesis
MH  - Middle Aged
MH  - Monocytes/*immunology
MH  - NF-kappa B/analysis
MH  - RNA, Messenger/analysis
MH  - Receptors, Cell Surface/biosynthesis
MH  - Toll-Like Receptor 2
MH  - Toll-Like Receptor 4
MH  - Toll-Like Receptors
EDAT- 2002/08/08 10:00
MHDA- 2002/10/11 04:00
CRDT- 2002/08/08 10:00
PHST- 2002/08/08 10:00 [pubmed]
PHST- 2002/10/11 04:00 [medline]
PHST- 2002/08/08 10:00 [entrez]
AID - S1521661602952538 [pii]
AID - 10.1006/clim.2002.5253 [doi]
PST - ppublish
SO  - Clin Immunol. 2002 Aug;104(2):191-8. doi: 10.1006/clim.2002.5253.