Circulating monocytes from systemic sclerosis patients with interstitial lung disease show an enhanced profibrotic phenotype.
Circulating monocytes from systemic sclerosis patients with interstitial lung disease show an enhanced profibrotic phenotype.
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DOI：
10.1038/labinvest.2010.73
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发表时间：
2010-06
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影响因子：
--
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中科院分区：
文献类型：
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Profibrotic cells derived from circulating CD14+ monocytes include fibrocytes and alternatively activated macrophages. These cells are associated with interstitial lung disease (ILD) and are implicated in the pathogenesis of Systemic Sclerosis (SSc); however, the simultaneous presence of profibrotic cells and their associated mediators in the circulation of these patients has not been defined. We hypothesized that monocytes from patients with SSc-related ILD (SSc-ILD) would show profibrotic characteristics when compared with normal controls. We recruited patients with SSc-ILD (n=12) and age-matched normal controls (n=27) and quantified circulating collagen producing cells by flow cytometry for CD45 and pro-Collagen I. The in vitro alternative activation potential of CD14+ monocytes was assessed using flow cytometry for the scavenger receptor CD163, and by ELISA for CCL18 and IL-10 secretion. Profibrotic mediators in plasma were quantified using Luminex-based assays. The concentration of circulating collagen producing cells was increased in the SSc-ILD patients when compared to controls. These cells were composed of both CD34+ fibrocytes and a population of CD34+CD14+ cells. Cultured CD14+ monocytes from SSc-ILD patients revealed a profibrotic phenotype characterized by expression of CD163 and by enhanced secretion of CCL18 and IL-10 in response to pro-inflammatory activation. Plasma levels of IL-10, MCP-1, IL-1RA, and TNF levels were significantly elevated in the plasma of the SSc-ILD cohort. Subgroup analysis of the normal controls revealed that unlike the subjects ≤ 35 years, subjects ≥ 60 years old showed higher levels of circulating CD34+CD14+ cells, collagen producing CD14+ monocytes, CD163+ monocytes, IL-4, IL-10, IL-13, MCP-1, and CCL-18. These data indicate that the blood of patients with SSc-ILD and of healthy aged controls is enriched for fibrocytes, profibrotic monocytes, and fibrosis-associated mediators. Investigations defining the factors responsible for this peripheral blood profile may provide new insight into SSc-ILD as well as the pathophysiology of aging.
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影响因子：
4.4
作者：
Martinez, Fernando O.;Gordon, Siamon;Mantovani, Alberto
通讯作者：
Mantovani, Alberto
DOI：
10.1016/j.jacr.2007.08.016
发表时间：
2008-01-01
期刊：
Journal of the American College of Radiology : JACR
影响因子：
--
作者：
Bucala, Richard
通讯作者：
Bucala, Richard
DOI：
10.1016/j.jtcvs.2004.10.035
发表时间：
2005-05-01
影响因子：
6
作者：
D'Ovidio, F;Mura, M;Keshavjee, S
通讯作者：
Keshavjee, S
影响因子：
5.1
作者：
Katebi, Majid;Fernandez, Patricia;Chan, Edwin S. L.;Cronstein, Bruce N.
通讯作者：
Cronstein, Bruce N.
影响因子：
5.5
作者：
Everhart, MB;Han, W;Blackwell, TS
通讯作者：
Blackwell, TS