期刊
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
卷 46, 期 5, 页码 607-613出版社
AMER THORACIC SOC
DOI: 10.1165/rcmb.2011-0231OC
关键词
macrophage heterogeneity; alpha-1 antitrypsin; macrophages; dendritic cells
资金
- Netherlands Asthma Foundation [3.2.08.0032]
alpha(1)-Antitrypsin (AAT) acts as an important neutrophil elastase inhibitor in the lung. Although the hepatocyte is considered to be the primary source of AAT, local production by monocytes, macrophages, and epithelial cells may contribute to the formation of an antielastase screen. Because monocytes can differentiate into a heterogeneous population of macrophages with subpopulations ranging from proinflammatory properties (M Phi-1) to antiinflammatory properties (M Phi-2) and into dendritic cells (DCs), we studied whether LPS, TNF-alpha, and oncostatin M (OSM) enhance AAT production differentially in cultured M Phi-1, M Phi-2, and DCs. Monocytes from healthy blood donors were cultured for 7 days in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor, or GM-CSF with IL-4 to obtain M Phi-1, M Phi-2, and immature (i) DCs, respectively. Cells were stimulated with LPS, TNF-alpha, or OSM, and AAT synthesis was assessed by quantitative RT-PCR, immunocytochemistry, and ELISA. Spontaneous release of AAT was higher in M Phi-1 than in M Phi-2 and iDCs, and only LPS significantly increased AAT production in M Phi-1, in M Phi-2, and DC. TNF-alpha and OSM did not affect AAT secretion. The secretion levels of the related protease inhibitors alpha-1 antichymotrypsin and secretory leukocyte proteinase inhibitor were below the limits of detection by ELISA. In contrast to the protein data, analysis by quantitative RT-PCR showed that 24-hour LPS exposure caused a maximal 21-fold AAT mRNA increase in M Phi-1, a 21-fold increase in M Phi-2, and an 11-fold increase in DCs. These data suggest that cellular differentiation is a regulator of local AAT production.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据