Document Detail


Expression of blood coagulation factors on monocytes after exposure to TNF-treated endothelium in a novel whole blood model of arterial flow.
MedLine Citation:
PMID:  19699743     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Activated blood monocytes are a major source of tissue factor (TF), the principal initiator of blood coagulation. TF can be shed from the monocyte surface in association with microparticles (MPs) and increased numbers of circulating MPs are indicative of poor clinical outcome in a number of inflammatory disorders, including atherosclerosis. The mechanisms coupling inflammation with aberrant TF production/activity remain obscure but the protease-activated receptor (PAR) family has been implicated. We have previously shown (i) that freshly isolated human monocytes express low levels of cell surface PAR-2, (ii) that cell surface PAR-2 is rapidly upregulated from intracellular stores following mechanical stimulation, and (iii) that PAR-2 stimulation results in elevation of intracellular calcium and cytokine release. Here, we have investigated the expression of PAR-2 on monocytes exposed to TNF-activated endothelial cells both under static conditions and in our newly-established model of arterial flow, using diluted whole blood. Monocyte surface PAR-2 expression was upregulated following static exposure to activated EC and with laminar (atheroprotective) arterial flow there was a further increase in monocyte PAR-2 expression. We have also shown under arterial flow conditions that exposure to TNF-stimulated EC resulted in a significant increase in expression of TF on monocytes compared to that on cells exposed to quiescent EC. These data strongly suggest that direct or indirect interactions with inflamed EC can modulate expression of PAR-2 and TF on the monocyte cell surface.
Authors:
Marion G Macey; Sabine I Wolf; Caroline P D Wheeler-Jones; Charlotte Lawson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-08-21
Journal Detail:
Title:  Journal of immunological methods     Volume:  350     ISSN:  1872-7905     ISO Abbreviation:  J. Immunol. Methods     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-14     Completed Date:  2009-11-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1305440     Medline TA:  J Immunol Methods     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  133-41     Citation Subset:  IM    
Affiliation:
Department of Haematology, The Royal London Hospital, Pathology and Pharmacy Building, 80, Newark Street, London E1 2ES, United Kingdom. marion.macey@bartsandthelondon.nhs.uk
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MeSH Terms
Descriptor/Qualifier:
Adult
Atherosclerosis / immunology,  metabolism*,  pathology
Blood Flow Velocity
Calcium / immunology,  metabolism
Cells, Cultured
Endothelium, Vascular / immunology,  metabolism*,  pathology
Female
Humans
Male
Models, Cardiovascular*
Monocytes / immunology,  metabolism*,  pathology
Receptor, PAR-2 / biosynthesis,  immunology
Thromboplastin / biosynthesis*,  immunology
Tumor Necrosis Factor-alpha
Up-Regulation / drug effects*,  immunology
Grant Support
ID/Acronym/Agency:
//British Heart Foundation
Chemical
Reg. No./Substance:
0/Receptor, PAR-2; 0/Tumor Necrosis Factor-alpha; 7440-70-2/Calcium; 9035-58-9/Thromboplastin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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