On the role of C1-inhibitor as inhibitor of tissue-type plasminogen activator in human plasma.
An enzyme immuno assay was developed to measure complexes of tissue-type plasminogen activator (t-PA) with C1-inhibitor in order to study the role of C1-inhibitor as an inhibitor of t-PA in plasma. In vitro experiments with melanoma and recombinant t-PA learned that purified C1-inhibitor reacts with both single chain t-PA and two chain t-PA. The rate constants ranged from 3.0 to 5.2 M-1s-1. In plasma, melanoma and recombinant two chain t-PA were hardly inhibited by C1-inhibitor, in contrast to melanoma and recombinant single chain t-PA which were inhibited to the same extent by endogenous C1-inhibitor as they were by purified C1-inhibitor. In vivo, t-PA/C1-inhibitor complex could be measured in plasma in a few cases in healthy volunteers (0.62 +/- 0.43 ng/ml t-PA equivalents), after exercise (0.84 +/- 0.25 ng/ml t-PA equivalents) and after a desmopression infusion (0.26 +/- 0.04 ng/ml t-PA equivalents). However, t-PA/C1-inhibitor complex was found in plasma in all cases after venous occlusion (1.7 +/- 0.5 ng/ml t-PA equivalents), in peritoneal fluid from patients suffering from peritoneal inflammatory disease (2.2 +/- 1.3 ng/ml t-PA equivalents) and in plasma from healthy volunteers during a t-PA infusion (27.7 +/- 18.5 ng/ml t-PA equivalents at peak level). In the last case, about 8% of the infused dose of recombinant t-PA (alteplase) was inhibited by C1-inhibitor at peak level.(ABSTRACT TRUNCATED AT 250 WORDS)
Huisman
L G
LG
Centre for Human Drug Research, Leiden, The Netherlands.
van Griensven
J M
JM
Kluft
C
C
D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology / Q000502:physiology*; D003250:Constriction; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006207:Half-Life; D006801:Humans; D008545:Melanoma / Q000473:pathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D010538:Peritonitis / Q000097:blood; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000097:blood; D014680:Veins / Q000502:physiology
D003174:Complement C1 Inactivator Proteins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D003894:Deamino Arginine Vasopressin