Expression of the α₁-proteinase inhibitor gene in human monocytes and macrophages

Expression of the α₁-proteinase inhibitor (α₁PI) gene was studied in human mononuclear cells. Using RNA blot and dot hybridization, α₁PI 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 α₁PI were demonstrated in human monocytes and macrophages, but not in lymphocytes. In addition, α₁PI was secreted in functionally active form as shown by complexing with serine proteases. Biosynthesis of α₁PI by mononuclear phagocytes was greatest during the first 24 hr in culture and progressively decreased over the next 10 days. The reduction in α₁PI biosynthesis in vitro involved a mechanism acting at the pretranslational level as α₁PI 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 α₁PI deficiencies and study of the functional significance of locally produced α₁PI in normal tissues and sites of injury or inflammation.