The cellular defect in alpha 1-proteinase inhibitor (alpha 1-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 alpha 1-proteinase inhibitor (alpha 1PI) in individuals with homozygous alpha 1PI deficiency (hereafter referred to as PiZZ), biosynthesis and secretion of alpha 1PI were studied in Xenopus oocytes microinjected with hepatic mRNA and in blood monocytes (an extrahepatic site of alpha 1PI gene expression). Although both the usual alpha 1PI (hereafter referred to as PiMM) and PiZZ alpha 1PI were secreted in functionally active form, the rate of secretion of alpha 1PI was significantly and selectively decreased in Xenopus oocytes injected with PiZZ liver mRNA and in monocytes from PiZZ individuals. The apparent size of alpha 1PI in the intracellular compartment of Xenopus oocytes injected with PiZZ liver mRNA was different from the corresponding intracellular PiMM alpha 1PI in oocytes injected with PiMM liver mRNA. There were also differences in the relative ratio of native and complexed alpha 1PI secreted by monocytes from individuals with PiMM and PiZZ phenotypes.
D000818:Animals; D001798:Blood Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D006720:Homozygote; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism*; D011480:Protease Inhibitors / Q000172:deficiency*; D012333:RNA, Messenger / Q000235:genetics*; D000515:alpha 1-Antitrypsin
D001798:Blood Proteins; D011480:Protease Inhibitors; D012333:RNA, Messenger; D000515:alpha 1-Antitrypsin