| ABSTRACT: |
|
Platelet factor 4 is a polypeptide constituent of platelet alpha
granules that is released during platelet aggregation and inhibits
heparin-mediated reactions. Hageman factor (factor XII) is a plasma
proenzyme that, when activated by certain negatively charged agents,
initiates clotting via the intrinsic pathway of thrombin formation. In
earlier studies using crude systems, platelet factor 4 inhibited
activation of Hageman factor by dextran sulfate or cerebrosides, but not
activation of Hageman factor by kaolin or ellagic acid. In the present
study we examined the mechanisms of inhibition by platelet factor 4, using
purified reagents. Platelet factor 4 inhibited activation of Hageman
factor by ellagic acid, as measured by amidolysis of a synthetic substrate
of activated Hageman factor, an effect inhibited by heparin or by an
anti-platelet factor 4 antiserum. Coating glass tubes with platelet factor
4 before addition of normal plasma significantly lengthened the partial
thromboplastin time of normal plasma. In addition, the clot-promoting
properties of kaolin were inhibited by its prior exposure to platelet
factor 4. Thus, the inhibitory properties of platelet factor 4 directed
against the activation of Hageman factor were confirmed in a purified
system. In this purified system, in contrast to earlier studies using
crude systems, platelet factor 4 inhibited activation of Hageman factor by
glass, ellagic acid, or kaolin. |