Evaluation of the S-type of alpha-1-antitrypsin as an in vivo and in vitro inhibitor of neutrophil elastase. Academic Article Article uri icon

Overview

MeSH

  • Adult
  • Dose-Response Relationship, Drug
  • Epithelium
  • Female
  • Haplotypes
  • Homozygote
  • Humans
  • Lung
  • Male
  • Oxidation-Reduction
  • Phenotype
  • Pulmonary Emphysema
  • Risk Factors
  • Time Factors
  • alpha 1-Antitrypsin Deficiency

MeSH Major

  • Neutrophils
  • Pancreatic Elastase
  • alpha 1-Antitrypsin

abstract

  • S-type alpha 1-antitrypsin (alpha 1AT) is a deficiency haplotype that differs from the common normal M1 (val213) alpha 1AT haplotype by a single amino acid (glu264 to val264). To evaluate the adequacy of the antineutrophil elastase protection associated with the S homozygous state, alpha 1AT plasma and lung epithelial lining fluid (ELF) levels and antineutrophil elastase function were analyzed in 9 PISS subjects. The plasma alpha 1AT levels of SS subjects were intermediate between that of M1M1 and ZZ subjects (p less than 0.001, all comparisons) and the plasma neutrophil elastase inhibitory capacity paralleled the differences in alpha 1AT concentration (p less than 0.001, all comparisons). The association rate constant for neutrophil elastase of the purified S protein was less than that of the normal molecule (S-type, 7.1 +/- 0.1 X 10(6) M-1 s-1; M1-type, 9.6 +/- 0.2 X 10(6) M-1 s-1; p less than 0.001), but much greater than that for the Z molecule (p less than 0.001). Exposure of the purified S protein to increasing oxidant burdens resulted in a dose-dependent reduction in the ability of the molecule to inhibit neutrophil elastase in a fashion parallel to that of the M1 and Z proteins. Quantification of ELF alpha 1AT levels and antineutrophil elastase capacity demonstrated that the SS ELF parameters were, as in plasma, intermediate between M1 homozygotes and Z homozygotes. Using the association rate constant together with the quantification of ELF alpha 1AT levels, the "in vivo lung inhibition time" was estimated, yielding an assessment of the relative antineutrophil elastase screen of the PISS lower respiratory tract.(ABSTRACT TRUNCATED AT 250 WORDS)

publication date

  • February 1988

has subject area

  • Adult
  • Dose-Response Relationship, Drug
  • Epithelium
  • Female
  • Haplotypes
  • Homozygote
  • Humans
  • Lung
  • Male
  • Neutrophils
  • Oxidation-Reduction
  • Pancreatic Elastase
  • Phenotype
  • Pulmonary Emphysema
  • Risk Factors
  • Time Factors
  • alpha 1-Antitrypsin
  • alpha 1-Antitrypsin Deficiency

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1164/ajrccm/137.2.364

PubMed ID

  • 3257660

Additional Document Info

start page

  • 364

end page

  • 370

volume

  • 137

number

  • 2