Document Detail


Identification of human thrombin-activatable fibrinolysis inhibitor in vascular and inflammatory cells.
MedLine Citation:
PMID:  21505719     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
TAFI (thrombin-activatable fibrinolysis inhibitor) is a carboxypeptidase zymogen originally identified in plasma. The TAFI pathway helps to regulate the balance between the coagulation and fibrinolytic cascades. Activated TAFI (TAFIa) can also inactivate certain pro-inflammatory mediators, suggesting that the TAFI pathway may also regulate communication between coagulation and inflammation. Expression in the liver is considered to be the source of plasma TAFI. TAFI has also been identified in platelets and CPB2 (the gene encoding TAFI) mRNA has been detected in megakaryocytic cell lines as well as in endothelial cells. We have undertaken a quantitative analysis of CPB2 mRNA and TAFI protein in extrahepatic cell types relevant to vascular disease. Using RT-PCR and quantitative RT-PCR, we detected CPB2 mRNA in the human megakaryoblastic cell lines MEG-01 and Dami, the human monocytoid cell line THP-1 as well as THP-1 cells differentiated into a macrophage-like phenotype, and in primary human umbilical vein and coronary artery endothelial cells. CPB2 mRNA abundance in MEG-01, Dami, and THP-1 cells was modulated by the state of differentiation of these cells. Using a recently developed TAFIa assay, we detected TAFI protein in the lysates of the human hepatocellular carcinoma cell line HepG2 as well as in MEG-01 and Dami cells and in the conditioned medium of HepG2 cells, differentiated Dami cells, and THP-1 macrophages. We have obtained clear evidence for extrahepatic expression of TAFI, which has clear implications for the physiological and pathophysiological functions of the TAFI pathway.
Authors:
J H H Lin; M Garand; B Zagorac; S L Schadinger; C Scipione; M L Koschinsky; M B Boffa
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Publication Detail:
Type:  Journal Article     Date:  2011-04-20
Journal Detail:
Title:  Thrombosis and haemostasis     Volume:  105     ISSN:  0340-6245     ISO Abbreviation:  Thromb. Haemost.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-07     Completed Date:  2011-10-27     Revised Date:  2012-01-10    
Medline Journal Info:
Nlm Unique ID:  7608063     Medline TA:  Thromb Haemost     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  999-1009     Citation Subset:  IM    
Affiliation:
Department of Chemistry & Biochemistry, University of Windsor, Windsor, Ontario, Canada.
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MeSH Terms
Descriptor/Qualifier:
Blood Coagulation
Endothelial Cells / metabolism*,  pathology
Fibrinolysis
Gene Expression Regulation
Hemostasis
Hep G2 Cells
Humans
Inflammation
Macrophages / metabolism*,  pathology
Megakaryocyte Progenitor Cells / metabolism*,  pathology
Membrane Glycoproteins / genetics,  immunology,  metabolism*
Vascular Diseases / blood,  genetics,  immunology*,  metabolism
Chemical
Reg. No./Substance:
0/Membrane Glycoproteins; 0/endoplasmic reticulum glycoprotein p72

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


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