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Culture of Macrophage Colony-stimulating Factor Differentiated Human Monocyte-derived Macrophages
Published on: June 30, 2016
Altered pattern of monocyte differentiation and monocyte-derived TGF-β1 in severe asthma
Chih-Hsing Hung1,2,3,4,5, Chin-Chou Wang6,7, Jau-Ling Suen3,5,8
1Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Abstract:
CD14+ monocytes contain precursors for macrophages and fibrocytes, known to be involved in regulating airway remodeling in human asthma and distinguishable by the PM-2K marker. We sought to identify circulating subsets of PM-2K+ macrophage-like cells and evaluate their relationships to lung function, severity and control status. Circulating PM-2K+ macrophage-like cells and fibrocytes could be identified and distinguished between normal individuals (N = 152) and asthmatic subjects (N = 133) using multi-parametric flow cytometry. PM-2K+ macrophage-like cells were found to be significantly lower in asthmatic subjects, particularly noted for the CD14-PM-2K+ subset and PM-2K+CCR7-CD86+ cells in subjects with poor lung function (FEV%/FVC% < 80%) as compared to those of normal subjects and asthmatics with normal lung function, whereas the frequency of fibrocytes was higher in asthmatics and the CCR7-CD86+ subset distribution was significantly different in subjects with varying severity. Moreover, exogenous transforming growth factor beta 1 (TGF-β1) was found to inhibit the generation of PM-2K+ macrophage-like cells, but promote the growth of fibrocytes, from CD14+ monocytes, and monocyte-derived TGF-β1 was found to correlate with the lung function, severity and control status in asthmatic patients. Collectively, aberrant differentiation of monocytes into PM-2K+ macrophage-like cell subsets and fibrocytes, together with increased monocyte-derived TGF-β1, characterized patients with severe asthma.
Insights
In asthma patients, circulating PM-2K+ macrophage-like cells are reduced, while fibrocytes increase. Monocyte-derived TGF-β1 also correlates with asthma severity and lung function decline.
Area of Science:
- Immunology
- Respiratory Medicine
- Cell Biology
Background:
- CD14+ monocytes are precursors to macrophages and fibrocytes, implicated in airway remodeling in asthma.
- The PM-2K marker distinguishes these cells, but their circulating subsets and roles in asthma remain unclear.
Purpose of the Study:
- To identify circulating PM-2K+ macrophage-like cell subsets in asthma.
- To evaluate the relationship between these subsets, fibrocytes, and asthma severity, lung function, and control status.
Main Methods:
- Multi-parametric flow cytometry was used to identify and distinguish circulating PM-2K+ macrophage-like cells and fibrocytes.
- Analysis included comparisons between normal individuals and asthmatic subjects with varying lung function and severity.
- The effect of transforming growth factor beta 1 (TGF-β1) on monocyte differentiation was investigated in vitro.
Main Results:
- Asthmatic subjects had significantly lower levels of PM-2K+ macrophage-like cells, especially the CD14-PM-2K+ subset.
- Reduced PM-2K+ macrophage-like cells and increased fibrocytes correlated with poorer lung function (FEV%/FVC% < 80%) and varying asthma severity.
- Exogenous TGF-β1 inhibited PM-2K+ macrophage-like cell generation while promoting fibrocyte growth; monocyte-derived TGF-β1 correlated with asthma status.
Conclusions:
- Aberrant monocyte differentiation into PM-2K+ macrophage-like cells and fibrocytes characterizes asthma.
- Increased monocyte-derived TGF-β1 is associated with severe asthma, poor lung function, and impaired control.
- These findings highlight potential diagnostic and therapeutic targets in asthma management.
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