Evaluation of recombinant DNA-directed E.coli produced alpha 1-antitrypsin as an anti-neutrophil elastase for potential use as replacement therapy of alpha 1-antitrypsin deficiency. Academic Article uri icon

Overview

MeSH

  • DNA
  • Humans
  • Kinetics
  • Plasmids
  • alpha 1-Antitrypsin Deficiency

MeSH Major

  • DNA, Recombinant
  • Escherichia coli
  • Neutrophils
  • Pancreatic Elastase
  • alpha 1-Antitrypsin

abstract

  • alpha 1-antitrypsin (alpha 1AT) deficiency is an inherited disorder almost always associated with the development of panacinar emphysema in the fourth to fifth decades. One source of alpha 1AT for chronic replacement therapy of such individuals is that produced by E.coli directed by a cDNA coding for the human alpha 1AT molecule. Using TG1(E.coli), an alpha 1AT molecule produced by E.coli transformed with the plasmid-expressing vector pTG922, the present study shows that recombinant DNA-directed E.coli-produced alpha 1AT is as an effective inhibitor of neutrophil elastase as alpha 1AT purified from plasma. Importantly, TG1(E.coli) inhibited human neutrophil elastase with an association rate constant of 1.3 +/- 0.4X10(7) M-1 sec-1, similar to that of normal plasma alpha 1AT (1.1 +/- 0.1, p greater than 0.2). Furthermore, when TG1(E.coli) was added to alpha 1AT-deficient plasma obtained from homozygous alpha 1AT type Z individuals, the TG1(E.coli) remained functional and augmented the anti-neutrophil elastase activity of the serum proportional to the amount of TG1(E.coli) added. These observations suggest that if sufficient amounts of recombinant DNA methodology-produced alpha 1AT molecules could be safely delivered to the alveolar structures of alpha 1AT-deficient individuals, they would function to protect the alveolar walls from elastolytic attack.

publication date

  • August 15, 1985

has subject area

  • DNA
  • DNA, Recombinant
  • Escherichia coli
  • Humans
  • Kinetics
  • Neutrophils
  • Pancreatic Elastase
  • Plasmids
  • alpha 1-Antitrypsin
  • alpha 1-Antitrypsin Deficiency

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 3896239

Additional Document Info

start page

  • 1177

end page

  • 1184

volume

  • 130

number

  • 3