Document Detail


Role of tissue factor in the maternal immunological attack of the embryo in the antiphospholipid syndrome.
MedLine Citation:
PMID:  19921475     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Recurrent fetal loss affects 1-5% of women of childbearing age. Immunological mechanisms may account for 40% of recurrent miscarriages, and in particular, the antiphospholipid syndrome (APS) appears to be implicated in 7-25% of the cases. Because antiphospholipid (aPL) antibodies have thrombogenic properties, fetal loss in patients with APS has been ascribed to thrombosis of placental vessels. However, we have shown that inflammation, specifically activation of complement with generation of the anaphylotoxin C5a, is an essential trigger of fetal injury. Thrombosis and inflammation are linked in many clinical conditions. Tissue factor (TF), the major cellular initiator of the coagulation protease cascade, plays important roles in both thrombosis and inflammation, and its expression is increased in patients with APS. Here we describe how TF, acting as a proinflammatory molecule, induces trophoblast injury and fetal death in a mouse model of APS. Importantly, we will discuss how TF contributes to C5a-induced oxidative burst in neutrophils leading to trophoblasts and fetal injury in APS. The finding that TF is an important effector in aPL-induced inflammation may allow the development of new therapies to abrogate the inflammatory loop caused by tissue factor and improve pregnancy outcomes in patients with aPL antibodies. Statins downregulate TF-induced inflammation and rescued the pregnancies in aPL-treated mice, suggesting they may be a good treatment for women with aPL-induced pregnancy complications.
Authors:
Guillermina Girardi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical reviews in allergy & immunology     Volume:  39     ISSN:  1559-0267     ISO Abbreviation:  Clin Rev Allergy Immunol     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-05     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9504368     Medline TA:  Clin Rev Allergy Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  160-5     Citation Subset:  IM    
Affiliation:
Department of Medicine, Weill Medical College of Cornell University, New York, NY, USA. guillerminagirardi@gmail.com
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