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Elevated kallikrein activity in plasma from stable liver transplant recipients

Academic Article
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Overview

authors

  • Hayashi, J.
  • Salomon, Daniel
  • Hugli, T. E.

publication date

  • 2002

journal

  • International Immunopharmacology  Journal

abstract

  • Extensive in vitro conversion of complement components C3 and C4 has been observed in EDTA plasma obtained from a number of stable orthotopic liver transplant recipients (LTR) [Clin. Chem. 45 (1999) 1190]. Consequently, we designed a chromogenic substrate (Ac-Ala-Gly-Leu-Thr-Arg-p-nitroanilide, AGLTR-pNA), based on the C1s cleavage site in complement component C4, in an attempt to identify the plasma proteinase(s) that cleaves C4 in vitro. Average peptidase activity in EDTA plasma obtained from stable LTR (n = 16) was significantly higher (P<0.01) than that in plasma from healthy non-transplant donors (n = 16). This peptidase activity was also detected using commercial substrates designed for specific coagulation proteinases. The plasma proteinase was not inhibited by hirudin, a thrombin inhibitor, but was inhibited by the plasma kallikrein inhibitor D-Phe-Phe-Arg-chloromethylketone, which fails to inhibit C1s. We concluded that the peptidase detected inLTR plasma, using chromogenic substrates including AGLTR-pNA, was plasma kallikrein. Western blot analysis confirmed the presence of kallikrein-alpha-2-macroglobulin complexes (alpha2M) in LTR plasmas. We also demonstrated that kallikrein was not the proteinase responsible for the in vitro cleavage of C4. Elevation of the plasma peptidase activity correlated significantly with recurrent hepatitis C virus (HCV) infection in these liver recipients with a P value <0.02. Significant correlation was not observed between complement activation (i.e. the C4a levels) and recurrent HCV infection (P>0.15); however, C4a levels did correlate with rejection (P<0.02). These results suggest that elevation in plasma peptidase activity and activation of complement do signal different pathological events in LTR, events that appear related to HCV-induced infection and immune tissue injury, respectively.

subject areas

  • Adult
  • Chromatography, Gel
  • Complement C4
  • Complement C4a
  • Female
  • Graft Rejection
  • Humans
  • Kallikreins
  • Liver Transplantation
  • Male
  • Middle Aged
  • Serine Proteinase Inhibitors
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Research

keywords

  • complement activation
  • liver transplantation
  • plasma kallikrein
  • plasma peptidase activity
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Identity

International Standard Serial Number (ISSN)

  • 1567-5769

Digital Object Identifier (DOI)

  • 10.1016/s1567-5769(02)00144-3

PubMed ID

  • 12469941
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Additional Document Info

start page

  • 1667

end page

  • 1680

volume

  • 2

issue

  • 12

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