Effect of advanced glycation end product-modified albumin on tissue factor expression by monocytes. Role of oxidant stress and protein tyrosine kinase activation.

Diabetes is associated with a hypercoagulable state that contributes to macrovascular complications, including cardiovascular events. The glycation reaction, a consequence of chronic hyperglycemia, has also been implicated in the pathogenesis of diabetic complications. Glycated proteins have receptors on monocytes and generate reactive oxygen species that can regulate the expression of a number of genes.

Induction of interleukin-1 and subsequent tissue factor expression by anti-proteinase 3 antibodies in human umbilical vein endothelial cells.

Objective: To assess the ability of anti-proteinase 3 (anti-PR3) classic antineutrophil cytoplasmic antibodies (cANCA) to stimulate endothelial expression of tissue factor (TF), which is the main initiator of the coagulation cascade that can lead to endothelial injury and thrombosis in patients with Wegener's granulomatosis.

Methods: Human umbilical vein endothelial cells (HUVEC) were grown to confluence and stimulated with affinity-purified anti-PR3 antibodies, Igs from healthy subjects, and endotoxin (lipopolysaccharide) as positive control.

Results: TF activity was generated in anti-PR3-stimulated cells, as shown by a chromogenic test.

Protein tyrosine kinase activation is required for LPS and PMA induction of tissue factor mRNA in human blood monocytes.

Tissue factor (TF) is a transmembrane glycoprotein which assembles with factor VIIa on cell surfaces to form a proteolytically active cofactor-enzyme complex; the TF/VIIa complex initiates the coagulation protease cascade. In response to bacterial lipopolysaccharide (LPS) and phorbol-12 myristate 13-acetate (PMA), monocytes synthesize and express TF on their surface. However, the mechanisms by which LPS and PMA activate TF synthesis by human blood monocytes are not fully understood.

Interleukin-10 and pentoxifylline inhibit C-reactive protein-induced tissue factor gene expression in peripheral human blood monocytes.

Fibrin deposition is an integral feature of the inflammatory response. In response to C-reactive protein (CRP), an acute-phase reactant, blood monocytes synthesize and express tissue factor (TF), the main initiator of blood coagulation. We report the inhibitory effect of interleukin 10 (IL-10) and that of pentoxifylline, a methyl xanthine derivative, on monocyte expression of TF activity, TF protein and TF mRNA in response to CRP.

Endotoxin-induced tissue factor in human monocytes is dependent upon protein kinase C activation.

Tissue factor (TF) is a transmembrane receptor which, in association with factors VII and VIIa, activates factor IX and X, thereby activating the coagulation protease cascades. In response to bacterial lipopolysaccharide (LPS) monocytes transcribe, synthesize and express TF on their surface. We investigated whether LPS-induced TF in human monocytes is mediated by protein kinase C (PKC) activation.