Identification of monoclonal antibodies that inhibit the function of protein C inhibitor. Evidence for heparin-independent inhibition of activated protein C in plasma.
Monoclonal antibodies specific for protein C inhibitor (PCI) partially blocked the inactivation of activated protein C (APC) in plasma, whereas in a purified system, the PCI activity could be completely blocked. The inactivation of APC in normal and in PCI-depleted plasma was similar in the absence of heparin. The addition of heparin did not change the rate of inactivation of APC in PCI-depleted plasma, whereas in normal plasma a rapid phase of inhibition of APC was followed by a slower phase of inhibition. The slower phase was identical to the rate of inhibition of APC in the absence of heparin. After incubation of normal plasma with a monoclonal antibody specific for PCI that blocked its activity, there was no difference in heparin-dependent or heparin-independent inhibition of APC. These results indicate that in the absence of heparin PCI is unable to inactivate APC in a plasma environment.
Meijers
J C
JC
Department of Haematology, University Hospital, Utrecht, The Netherlands.
Vlooswijk
R A
RA
Kanters
D H
DH
Hessing
M
M
Bouma
B N
BN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000494:pharmacology; D001780:Blood Coagulation Tests; D001798:Blood Proteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D006493:Heparin / Q000097:blood*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011480:Protease Inhibitors / Q000032:analysis* / Q000494:pharmacology; D011486:Protein C / Q000097:blood / Q000276:immunology*; D018046:Protein C Inhibitor
D000911:Antibodies, Monoclonal; D001798:Blood Proteins; D011480:Protease Inhibitors; D011486:Protein C; D018046:Protein C Inhibitor; D006493:Heparin