Chapter category: Coagulation
Blood Borne Tissue Factor (Including Microparticles)
Molecular Mechanisms of Disseminated Intravascular Coagulation
Edited by: Hugo ten CateISBN: 1-58706-058-2
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Chapter authors:
Bjarne Østerud and Erik Bjørklid
Minor amounts of biologically active tissue factor (TF) are always constitutively present in circulating blood of healthy individuals. In various diseases, including those underlying the induction of disseminated intravascular coagulation (DIC), the level of circulating TF may be subject to changes due to production or release of the factor from peripheral monocytes or subendothelial structures. Thus TF will emerge on the surface of monocytes upon synthesis induction and become available from the subendothelium subsequent to permeability changes or damage to the endothelium. In subendothelial strata significant amounts of TF are constitutively present in fibroblasts, pericytes and macrophages.
Several pathophysiological conditions are associated with monocyte activation and ensuing TF expression. The degree to which TF activity is expressed strongly hinges on a P-selectin dependent interaction between monocytes, platelets and granulocytes. Part of the role of the latter two cell types is believed to entail a decryption process, unfolding to its full potential the TF activity of circulating monocytes, of which otherwise about 80% is encrypted and not available at the cell surface. Monocyte derived TF rich microparticles possessing P-selectin glycoprotein ligand1 (PSGL-1) either bind to activated platelets or to platelet derived microparticles expressing P-selectin, in the process generating a favorable microenvironment for TF activity expression. Alternatively selectin-ligand interactions may facilitate the generation of active TFcontaining hybrid microparticles of monocyte and platelet origin. The recent reports on TF localized on granulocytes are probably dealing not with TF originating in granulocytes per se, but rather with granulocyte-bound TF rich platelet/monocyte derived microparticles.
Although endothelial cells (EC) have been shown to synthesize large amounts of TF in vitro, it is the opinion of the authors that evidence is pending for any relevance of this observation to the in vivo situation. Rather the TF observed in association with the endothelium probably corresponds to TF rich monocyte derived microparticles bound to activated endothelial cells. In conclusion the phenomena observed thus far are best accounted for by monocytes serving as the sole TF synthesizing cell in the peripheral circulation.
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