The cellular defect in α₁-proteinase inhibitor (α₁-PI) deficiency is expressed in human monocytes and in Xenopus oocytes injected with human liver mRNA

To determine the basis for low serum concentrations of α₁-proteinase inhibitor (α₁PI) in individuals with homozygous α₁-PI deficiency (hereafter referred to as PiZZ), biosynthesis and secretion of α₁PI were studied in Xenopus oocytes microinjected with hepatic mRNA and in blood monocytes (an extrahepatic site of α₁PI gene expression). Although both the usual α₁PI (hereafter referred to as PiMM) and PiZZ α₁PI were secreted in functionally active form, the rate of secretion of α₁PI was significantly and selectively decreased in Xenopus oocytes injected with PiZZ liver mRNA and in monocytes from PiZZ individuals. The apparent size of α₁PI in the intracellular compartment of Xenopus oocytes injected with PiZZ liver mRNA was different from the corresponding intracellular PiMM αPI in oocytes injected with PiMM liver mRNA. There were also differences in the relative ratio of native and complexed α₁PI secreted by monocytes from individuals with PiMM and PiZZ phenotypes.