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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2423-2431. Prepublished online as a Blood First Edition Paper on May 29, 2007; DOI 10.1182/blood-2007-01-070631. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-01-070631v1 110/7/2423    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Redecha, P. Articles by Girardi, G. Search for Related Content PubMed PubMed Citation Articles by Redecha, P. Articles by Girardi, G. Related Collections Free Research Articles Hemostasis, Thrombosis, and Vascular Biology Immunobiology Phagocytes Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody–induced fetal injury Patricia Redecha1, Rachel Tilley2, Michael Tencati2, Jane E. Salmon1, Daniel Kirchhofer3, Nigel Mackman2, and Guillermina Girardi1 1 Hospital for Special Surgery–Department of Medicine, Weill Medical College of Cornell University, New York, NY; 2 Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA; 3 Department of Protein Engineering, Genentech, South San Francisco, CA Fetal loss in patients with antiphospholipid (aPL) antibodies 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. In this study, we analyzed the role of the procoagulant molecule tissue factor (TF) in a mouse model of aPL antibody–induced pregnancy loss. We found that either blockade of TF with a monoclonal antibody in wild-type mice or a genetic reduction of TF prevented aPL antibody–induced inflammation and pregnancy loss. In response to aPL antibody–generated C5a, neutrophils express TF potentiating inflammation in the deciduas and leading to miscarriages. Importantly, we showed that TF in myeloid cells but not fetal-derived cells (trophoblasts) was associated with fetal injury, suggesting that the site for pathologic TF expression is neutrophils. We found that TF expression in neutrophils contributes to respiratory burst and subsequent trophoblast injury and pregnancy loss induced by aPL antibodies. The identification of TF as an important mediator of C5a-induced oxidative burst in neutrophils in aPL-induced fetal injury provides a new target for therapy to prevent pregnancy loss in the antiphospholipid syndrome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Tissue factor needs a "complement" Keith R. McCrae Blood 2007 110: 2228. [Full Text] [PDF] This article has been cited by other articles: K. Kambas, M. M. Markiewski, I. A. Pneumatikos, S. S. Rafail, V. Theodorou, D. Konstantonis, I. Kourtzelis, M. N. Doumas, P. Magotti, R. A. DeAngelis, et al. C5a and TNF-{alpha} Up-Regulate the Expression of Tissue Factor in Intra-Alveolar Neutrophils of Patients with the Acute Respiratory Distress Syndrome J. Immunol., June 1, 2008; 180(11): 7368 - 7375. [Abstract] [Full Text] [PDF] J. Salmon and P. de Groot Pathogenic role of antiphospholipid antibodies Lupus, May 1, 2008; 17(5): 405 - 411. [Abstract] [PDF]

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