Expression of the alpha 1-proteinase inhibitor gene in human monocytes and macrophages.

Abstract

Expression of the .alpha.1-proteinase inhibitor (.alpha.1PI) gene was studied in human mononuclear cells. Using RNA blot and dot hybridization, .alpha.1PI mRNA was detected in human peripheral blood monocytes, bronchoalveolar and breast milk macrophages, but not in B or T lymphocytes. Using incorporation of a radiolabeled amino acid precursor, synthesis and secretion of .alpha.1PI were demonstrated in human monocytes and macrophages, but not in lymphocytes. .alpha.1PI was secreted in functionally active form as shown by complexing with serine proteases. Biosynthesis of .alpha.1PI by mononuclear phagocytes was greatest during the first 24 h in culture and progressively decreased over the next 10 days. The reduction in .alpha.1PI biosynthesis in vitro involved a mechanism acting at the pretranslational level as .alpha.1PI mRNA content also progressively declined over 10 days in culture. The ease of sampling human monocytes and macrophages now permits examination of the biochemical defect in homozygous PiZ and PiS .alpha.1PI deficiencies and study of the functional significance of locally produced .alpha.1PI in normal tissues and sites of injury or inflammation.