Clearance of human native, proteinase-complexed, and proteolytically inactivated C1-inhibitor in rats.
C1-inhibitor is the only known inhibitor of the classical pathway of complement and the major inhibitor of the contact pathway of coagulation. Like other serine proteinase inhibitors, C1-inhibitor can exist in three conformations, ie, the native, the proteinase-complexed, and the proteolytically inactivated form. Here we studied the plasma elimination kinetics of these three forms of human C1-inhibitor in rats. The clearance of the complexed form of C1-inhibitor appeared to be the most rapid and depended in part on the proteinase involved (observed plasma t1/2 was 20 minutes for C1s-C1-inhibitor, 32 minutes for kallikrein-C1-inhibitor, and 47 minutes for beta XIIa-C1-inhibitor), whereas that of native C1-inhibitor was the slowest (observed plasma t1/2 4.5 hours). Inactivated C1-inhibitor was cleared with an apparent plasma t1/2 of 1.6 hours. Thus, the short plasma t1/2 of complexed relative to native C1-inhibitor explains why in patients only low concentrations of C1-inhibitor complexes may be observed despite activation of the contact and/or complement systems.
de Smet
B J
BJ
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
de Boer
J P
JP
Agterberg
J
J
Rigter
G
G
Bleeker
W K
WK
Hack
C E
CE
D000818:Animals; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism*; D010450:Endopeptidases / Q000097:blood*; D015956:Factor XIIa / Q000378:metabolism; D005260:Female; D006207:Half-Life; D007610:Kallikreins / Q000378:metabolism; D007700:Kinetics; D051381:Rats; D017208:Rats, Wistar
D003174:Complement C1 Inactivator Proteins; D010450:Endopeptidases; D007610:Kallikreins; D015956:Factor XIIa