In vivo and in vitro complexes of activated protein C with two inhibitors in baboons

F. Espana, A. Gruber, M. J. Heeb, S. R. Hanson, L. A. Harker, J. H. Griffin

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

In vivo complex formation of activated protein C with protein C inhibitor (APC-PCI) and with α1-antitrypsin (APC-α1AT) following infusion of 0.25 or 1.0 mg APC/kg in 1 hour into baboons was studied using immunoblotting and sandwich enzyme-linked immunosorbent assay (ELISA)s. Before APC infusion, detectable plasma levels (about 30 ng/mL) of APC-α1AT complex were found in the baboon plasma. At the lower APC dose, APC-PCI and APC-α1AT complex levels were 1.4 ± 0.3 (mean ± SD) and 0.8 ± 0.1 μg/mL after 1 hour of infusion. At the higher APC dose, the APC-PCI level was similar to the APC-α1AT level during the first 30 minutes, but after 1 hour of infusion the APC-α1AT level was higher than the APC-PCI level, reaching 4.1 ± 1.2 and 2.9 ± 1.2 μg/mL, respectively. After 24 hours, complex levels had returned to basal conditions. During infusion of protein C (1.0 mg/kg in 1 hour), both complexes were detected in low concentrations. Following bolus injection of APC, half-lives (t( 1/2 )) for APC and APC-PCI and APC-α1AT complexes of 10, 40, and 140 minutes, respectively, were observed. After 1-hour incubation with 2.5 μg/mL APC, baboon plasma contained 1.0 ± 0.2 and 0.8 ± 0.1 μg/mL of APC-PCI and APC-α1AT, respectively. Addition of 10 μg/mL APC to baboon plasma yielded 2.5 and 2.4 μg/mL APC-PCI and APC-α1AT after 1 hour, respectively. Immunoblotting analysis also showed in vivo formation of complexes of APC with an auxiliary inhibitor but not in vitro in citrated plasma. These data show that both PCI and α1AT are physiologic inhibitors of APC and suggest that when PCI is depleted by a high dose of APC, α1AT becomes the major inhibitor of APC.

Original languageEnglish (US)
Pages (from-to)1754-1760
Number of pages7
JournalBlood
Volume77
Issue number8
DOIs
StatePublished - 1991

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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