Truncated and microparticle-free soluble tissue factor bound to peripheral monocytes preferentially activate factor VII
Mohammad M. H. Khan1 *, Takashi Hattori *1, Stefan Niewiarowski 2, L. Henry Edmunds Jr. 1, Robert W. Colman 2
1 From the Harrison Department of Surgical Research, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA 2 The Sol Sherry Thrombosis Research Center, Hematology Division of the Department of Medicine, Temple University, Phil
Platelets, thrombin, Soluble tissue factor, monocytes
Soluble plasma tissue factor (TF) circulates in picomolar concentrations in healthy individuals and increases in a wide spectrum of diseases.This study tests the hypothesis that both truncatedTF (rsTF) or soluble plasmaTF (pTF) in low concentration combine with monocytes or platelets to convert factorVII (fVII) to fVIIa. Both rsTF (33 kDa) and pTF (47 kDa), obtained from pericardial wounds of patients having cardiac surgery using cardiopulmonary bypass (CPB), were studied in association with blood cells and TF-bearing microparticles. Tissue factor was measured by ELISA. RsTF binds to erythrocytes, platelets, mononuclear cells and polymorphoneutrophils.The rate of fVII conversion with rsTF (1–103 nM) is highest with mononuclear cells, less with platelets, minimal with polymorphoneutrophils and undetectable with erythrocytes. Either stimulated or unstimulated mononuclear cells or platelets in the presence of 3.5 pM rsTF or pTF convert fVII (10 nM) to fVIIa, but the amounts of fVIIa produced differ.When leukocytes or platelets are absent, microparticles associated with 3.5 pM TF antigen derived from pericardial wound plasma do not activate fVII. Stimulated mononuclear cells convert nearly all available fVII (10 nM) to fVIIa with 3.5 nM pTF; unstimulated mononuclear cells convert small amounts of fVII with 1 pM rsTF. In all comparisons mononuclear cells more efficiently convert fVII to fVIIa than do platelets.This study shows that stimulated mononuclear cells provide the most efficient platform for activation of rsTF or pTF at low concentrations of TF antigen.