Mechanisms of autoantibody-induced monocyte tissue factor expression.
The expression of tissue factor (TF) activity to flowing blood is the trigger for physiological coagulation as well as many types of thrombosis. A growing body of evidence suggests that increased tissue factor activity is a significant contributor towards the hypercoagulability associated with the antiphospholipid syndrome (APS). The increase in tissue factor activity appears to be due to increased transcription and translation of nascent tissue factor molecules but is not due to de-encryption of existing tissue factor molecules on cells. Autoantibodies and/or immune complexes circulating in APS patients appear to enhance the expression of tissue factor activity on monocytes and endothelial cells. Anti-beta2-glycoprotein I (beta2GPI) autoantibodies have been specifically implicated in the antibody-mediated enhancement of tissue factor activity. The presence of antibodies against tissue factor pathway inhibitor (TFPI) in certain APS patients suggests that negative regulation of tissue factor activity might also be impaired in these patients. Given a mechanism involving increased tissue factor activity in APS-associated thrombosis, agents specifically targeting tissue factor activity may be a novel and efficacious therapy that is safer than current approaches to the management of APS.
Wolberg
Alisa S
AS
Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, CB #7280, Rm. 3330 Thurston Building, Chapel Hill, NC 27599-7280, USA.
Roubey
Robert A S
RA
D016736:Antiphospholipid Syndrome / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000737:chemistry*; D005260:Female; D006023:Glycoproteins / Q000737:chemistry; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D013925:Thromboplastin / Q000096:biosynthesis*; D013927:Thrombosis; D053482:beta 2-Glycoprotein I
D001323:Autoantibodies; D006023:Glycoproteins; D008074:Lipoproteins; D053482:beta 2-Glycoprotein I; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin