Source:http://linkedlifedata.com/resource/pubmed/id/20404807
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2010-5-28
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pubmed:abstractText |
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 normal controls (n=27) and quantified circulating collagen-producing cells by flow cytometry for CD45 and pro-collagen I. The in vitro activation potential of CD14+ monocytes in response to lipopolysaccharide was assessed using flow cytometry for 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 with 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 proinflammatory 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 < or =35 years, subjects > or =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 CCL18. 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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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1530-0307
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pubmed:author |
pubmed-author:Antin-OzerkisDanielle EDE,
pubmed-author:BucalaRichard JRJ,
pubmed-author:GulatiMriduM,
pubmed-author:HerzogErica LEL,
pubmed-author:MathaiSusan KSK,
pubmed-author:MontgomeryRuth RRR,
pubmed-author:MurrayLynne ALA,
pubmed-author:PengXueyanX,
pubmed-author:ReilkoffRonald A SRA,
pubmed-author:RubinowitzAmi NAN,
pubmed-author:RussellThomas RTR,
pubmed-author:ShawAlbert CAC,
pubmed-author:SinerJonathan MJM
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pubmed:issnType |
Electronic
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pubmed:volume |
90
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
812-23
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pubmed:meshHeading |
pubmed-meshheading:20404807-Adult,
pubmed-meshheading:20404807-Antigens, CD14,
pubmed-meshheading:20404807-Antigens, CD45,
pubmed-meshheading:20404807-Cell Differentiation,
pubmed-meshheading:20404807-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:20404807-Flow Cytometry,
pubmed-meshheading:20404807-Humans,
pubmed-meshheading:20404807-Lung Diseases, Interstitial,
pubmed-meshheading:20404807-Macrophages, Alveolar,
pubmed-meshheading:20404807-Monocytes,
pubmed-meshheading:20404807-Pulmonary Fibrosis,
pubmed-meshheading:20404807-Scleroderma, Systemic
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pubmed:year |
2010
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pubmed:articleTitle |
Circulating monocytes from systemic sclerosis patients with interstitial lung disease show an enhanced profibrotic phenotype.
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pubmed:affiliation |
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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