Document Detail


Alpha-1 Antitrypsin Production by Pro- and Anti-Inflammatory Macrophages and Dendritic Cells.
MedLine Citation:
PMID:  22162908     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Alpha-1 antitrypsin (AAT) acts as an important neutrophil elastase inhibitor in the lung. Although the hepatocyte is considered as the primary source of AAT, local production by monocytes, macrophages and epithelial cells may contribute to the formation of an anti-elastase screen. Since monocytes can differentiate into a heterogeneous population of macrophages with subpopulations ranging from pro-inflammatory properties (MΦ-1) to anti-inflammatory properties (MΦ-2) and into dendritic cells (DC), we studied whether lipopolysaccharide (LPS), tumor necrosis factor alpha (TNFα) and oncostatin M (OSM) enhance AAT production differentially in cultured MΦ-1, MΦ-2 and DC. Monocytes from healthy blood donors were cultured for 7 days in the presence of GM-CSF, M-CSF, or GM-CSF and IL-4 to obtain MΦ-1, MΦ-2 and immature(i)DC, respectively. Next, cells were stimulated with LPS, TNFα or OSM and synthesis of AAT was assessed by quantitative RT-PCR, immunocytochemistry and ELISA. Spontaneous release of AAT was higher in MΦ-1 than in MΦ-2 and iDC and only LPS significantly increased AAT production in MΦ-1, MΦ-2 and DC, whereas TNFα and OSM did not affect AAT secretion. The secretion levels of the related protease inhibitors alpha-1 antichymotrypsin (ACT) and secretory leucocyte proteinase inhibitor (SLPI) were below the limits of detection by ELISA. In contrast to the protein data, analysis by quantitative RT-PCR showed that 24h LPS exposure caused a maximal 2.1-fold AAT mRNA increase in MΦ-1, a 21-fold increase in MΦ-2 and 11-fold increase in DC. These data suggest that cellular differentiation is a regulator of local AAT production.
Authors:
Emily F A van 't Wout; Annemarie van Schadewijk; Nigel D L Savage; Jan Stolk; Pieter S Hiemstra
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-8
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  -     ISSN:  1535-4989     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pulmonology, Leiden University Medical Center, Leiden, Netherlands.
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