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Inhibition and complexation of activated protein C by two major inhibitors
in plasma
MJ Heeb, F Espana and JH Griffin
Department of Immunology, Research Institute of Scripps Clinic, La Jolla,
CA 92037.
To determine the major physiologic inhibitors of activated protein C (APC),
plasma was incubated with APC or with Protac C and subjected to
immunoblotting. APC:inhibitor complexes gave two major bands reacting with
antiprotein C antibodies when immunoblotted on nondenaturing gels, and
additional minor bands that varied between serum and plasma. Formation of
one of the two major bands of APC:inhibitor complex, but not the other, was
stimulated by heparin and only this band reacted with antibodies to the
previously described APC inhibitor that is here designated PCI-1. Plasma
immunodepleted of PCI-1 formed complexes with APC as visualized with
antiprotein C but not anti-PCI-1 antibodies, and exhibited
heparin-independent inhibition of APC activity, providing evidence for the
existence of a second major physiologic APC inhibitor, PCI-2. Formation of
APC:PCI-2 complexes in PCI-1-depleted plasma paralleled inhibition of APC
amidolytic activity. PCI-2 was separated from PCI-1 and partially purified
using column chromatography. PCI-2 formed inactive complexes of
approximately 110,000 molecular weight (mol wt) with APC suggesting PCI-2
has an approximate mol wt of 50,000. Thus, inhibition of APC in plasma
involves two major distinct 50,000 mol wt inhibitors, the heparin-dependent
PCI-1 and the heparin- independent PCI-2.
Volume 73,
Issue 2,
pp. 446-454,
02/01/1989
Copyright © 1989 by The American Society of Hematology
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