Analysis of the serine protease function of porcine factor I produced by liver cells for xenotransplantation

Transpl Immunol. 2008 Apr;19(1):30-6. doi: 10.1016/j.trim.2007.11.003. Epub 2007 Dec 31.

Abstract

The use of a bioartificial liver with pig liver cells in the treatment of fulminant hepatic failure has already begun as a clinical trial in several countries. Therefore, studies on plasma complement regulatory proteins of the pig are necessary, because the liver produces them. Complement factor I is a serine protease that cleaves C3b and C4b. The DNA sequences of factor I have been reported in many species, with the noted exception of pigs. In this study, porcine factor I was cloned and an open reading frame of 1794 base pairs were identified. The predicted amino acid sequence maintained a relatively high homology compared to those of other mammals, especially in the serine protease (SP) region. The cell membrane-bound forms of the porcine and the human SP domain of factor I were constructed. Amelioration of complement-mediated cell lysis by these molecules was then tested, using several kinds of sera and Chinese hamster ovary (CHO) cell transfectants. Both molecules had a suppressing effect on pig, human and dog complements, indicating little species-specificity. Further studies of other plasma complement regulatory proteins produced from pig liver cells will need to be considered as the primary feature of the pig bioartificial liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • CHO Cells
  • Cloning, Molecular
  • Complement Factor I / chemistry
  • Complement Factor I / genetics
  • Complement Factor I / immunology*
  • Complement Factor I / metabolism*
  • Complement System Proteins / immunology
  • Complement System Proteins / metabolism
  • Cricetinae
  • Cricetulus
  • Dogs
  • Hepatocytes / immunology*
  • Hepatocytes / metabolism
  • Humans
  • Molecular Sequence Data
  • Sequence Alignment
  • Serine Endopeptidases / immunology
  • Serine Endopeptidases / metabolism
  • Species Specificity
  • Swine / immunology*
  • Transplantation, Heterologous

Substances

  • Complement System Proteins
  • Serine Endopeptidases
  • Complement Factor I