Induction of tissue factor activity in endothelial cells and monocytes by a modified form of albumin present in normal human plasma

Abstract

Molecules that induce tissue factor expression by responsive cells such as endothelial cells and monocytes may be important in the regulation of hemostasis and, perhaps, in mediating certain hemostatic disorders. A constituent of normal human plasma capable of inducing tissue factor activity in human endothelial cells and monocytes has been isolated and identified as a derivative of, or modification associated with albumin. Procoagulant albumin caused a concentration-dependent induction of tissue factor expression by human endothelial cells, but bovine endothelial cells were unresponsive. The dose-response curve developed a plateau phase, indicating that the capacity of endothelial cells to respond to the stimulus was finite. The maximum response induced by the procoagulant albumin was similar to that observed for maximally effective concentrations of endotoxin, interleukin-1, and tumor necrosis factor. Time-course studies showed that procoagulant albumin produced peak activity in 4 to 6 hours. Identification of a procoagulant form of albumin in normal human plasma suggests a potential role for this constituent in regulation of hemostasis.

Anticoagulant action of low, physiologic, and high albumin levels in whole blood

“…This apparent procoagulant action of albumin, however, cannot be attributed to the presence of the previously described “procoagulant albumin”. Procoagulant albumin has been shown to support coagulation by inducing TF expression in endothelial cells and monocytes but we measured thrombin generation in PPP samples lacking these cells [ 37 ]. To our knowledge, the underlying mechanisms of the procoagulant properties of albumin in PPP samples are missing so far.…”

Procoagulant Albumin Increases Vascular Endothelial Cell Prostacyclin Secretion

“…The supemate was dialyzed overnight against 10 mM NaCl, 10 mM Tris, pH 8.0 buffer, then applied to a Mono-Q anion-exchange column. Frac tions eluting at 250-350 mM NaCl were assayed for tissue factor-inducing activity in a bioassay (10). Fractions with maximal activity were dialyzed against 150 mM NaCl, 20 mM Tris, pH 7.4 and were used in the present expe riments.…”

“…Active fractions were characterized by tissue factor-inducing activity in a bioassay (10) using HUVEC and a chromogenic substrate method. HUVEC were first incubated with Medium 199 (0.4 ml) and column fraction (0.1 ml) for 4 h, then washed and incubated with phenol-free Medium 199 (0.45 ml), Factor Xa substrate (0.05 ml) and Proplex-T (0.01 ml, source of Factors VII and X).…”

“…Our laboratory has isolated and characterized a constituent of normal human plasma that originally was demonstrated to induce tissue factor activity in human endothelial cells and monocytes (10). This plasma protein was identified as an anionic form of albumin that we termed procoagulant albumin (P-AI).…”

Identity of the tissue factor‐inducing activity in human plasma

“…Several years ago, we observed a similar phenomenon in which normal plasma induced TF activity in human endothelial cells and monocytes. The active component of plasma was identified as a modified (anionic) form of albumin that we called procoagulant albumin (Faucette et al , 1992). No change in TF‐inducing activity was seen in plasma samples from patients with a variety of disorders (Grosset et al , 1994).…”