A lymphokine regulates expression of alpha-1-proteinase inhibitor in human monocytes and macrophages

S. Takemura, T. H. Rossing, D. H. Perlmutter

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Biosynthesis and secretion of alpha-1-proteinase inhibitor (α1PI) has been demonstrated in primary cultures of human mononuclear phagocytes, making it possible to study regulation of α1PI in normal (PiMM) and homozygous-deficient (PiZZ) individuals. In this study, expression of α1PI by blood monocytes, bronchoalveolar, and breast milk macrophages decreased during 1 wk in culture whereas expression of other secreted proteins increased. The addition of crude supernatants from mitogen-stimulated peripheral blood mononuclear cells to confluent monolayers of mononuclear phagocytes after 1 wk in culture resulted in a 2- to 2.5-fold increase in α1PI expression. The increase in α1PI expression was dose- and time-dependent, and involved a mechanism acting at a pretranslational level as shown by an increase in specific messenger RNA content corresponding to the increase in synthesis and secretion of α1PI. Although α1PI was expressed in native form and in forms complexed with serine protease by monocytes early in culture, it was expressed in its native form alone when monocytes were incubated with the lymphokine after 1 wk in culture. The regulating factor had the characteristics of a polypeptide and was derived from T lymphocytes, but it was not interferon-alpha, -beta, -gamma, or interleukin 2. This lymphokine also stimulated synthesis of α1PI in monocytes of homozygous-deficient PiZZ individuals, but had minimal effect on secretion, thereby increasing the intracellular accumulation of the inhibitor and exaggerating the defect in secretion of α1PI in these individuals. Regulation of mononuclear phagocyte α1PI expression by a lymphokine provides a model for further analysis of the effect of enhanced synthesis on a defect in posttranslational processing/secretion and for analysis of differential regulation of protease and inhibitor expressed in the same cells.

Original languageEnglish
Pages (from-to)1207-1213
Number of pages7
JournalJournal of Clinical Investigation
Volume77
Issue number4
DOIs
StatePublished - 1986

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