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Generation of Human Monocyte-derived Dendritic Cells from Whole Blood
Published on: December 24, 2016
Expression of LAIR-1 (CD305) on Human Blood Monocytes as a Marker of Hepatic Cirrhosis Progression
María Martínez-Esparza1, Antonio José Ruiz-Alcaraz1, Violeta Carmona-Martínez1
1Departamento de Bioquímica, Biología Molecular (B) e Inmunología, Facultad de Medicina, IMIB and Regional Campus of International Excellence "Campus Mare Nostrum", Universidad de Murcia, 30100 Murcia, Spain.
Insights
Monocyte LAIR-1 (leukocyte-associated immunoglobulin-like receptor 1) expression is elevated in liver cirrhosis, potentially serving as an early biomarker for liver damage. Macrophage expression in the liver was decreased in cirrhosis.
Area of Science:
- Immunology
- Hepatology
- Cell Biology
Background:
- The inhibitory receptor LAIR-1 (CD305) is implicated in inflammatory responses.
- Its role in chronic inflammatory diseases like liver cirrhosis warrants investigation.
- This study focuses on LAIR-1 expression in liver macrophages and blood monocytes during cirrhosis progression.
Purpose of the Study:
- To investigate the expression of LAIR-1 on liver macrophages and blood monocytes in relation to liver cirrhosis progression.
- To determine if LAIR-1 expression can serve as a biomarker for early detection of liver damage.
Main Methods:
- Immunohistochemistry
- Flow cytometry
- Western blot analysis of LAIR-1 expression.
- In vitro studies using HL-60 macrophages and human blood monocytes.
Main Results:
- Decreased LAIR-1 expression on liver macrophages in cirrhotic livers, potentially due to collagen interference.
- In vitro studies showed decreased LAIR-1 expression after differentiation and increased total content (not surface) after activation in macrophages.
- Blood monocytes from cirrhotic patients showed significantly higher LAIR-1 expression across all subsets, particularly in intermediate monocytes.
- In vitro monocyte activation did not increase surface LAIR-1, suggesting in vivo stimuli are crucial for the observed increase in cirrhosis.
Conclusions:
- Elevated monocyte LAIR-1 expression in liver cirrhosis is a unique finding compared to other chronic inflammatory conditions.
- Monocyte LAIR-1 expression may represent a novel biomarker for the early detection of liver damage in liver cirrhosis.
Background And Aim:
The presumed role of the inhibitory receptor LAIR-1 (CD305) in the inflammatory response suggests that it might contribute to the pathophysiology of chronic inflammatory diseases such as liver cirrhosis. We studied the LAIR-1 expression on liver macrophages and blood monocytes related to the progression of liver cirrhosis.
Methods:
The expression of LAIR-1 was analyzed by immunohistochemistry, flow cytometry, and Western blot.
Results:
We found a decreased number of macrophages expressing LAIR-1 in cirrhotic liver that could be due to a high presence of collagen, ligand of LAIR-1, in the fibrotic tissue which could downregulate its expression or interfere with the immunostaining. The expression of LAIR-1 decreased after cell differentiation, and the total content, but not the cell surface expression, increased after activation in the HL-60 human macrophage in vitro model. Blood monocytes exhibited higher LAIR-1 expression levels in cirrhotic patients, which were evident even in early clinical stages in all monocyte subsets, and greater in the "intermediate" inflammatory monocyte subpopulation. The in vitro activation of human blood monocytes did not increase its expression on the cell surface suggesting that the in vivo increase of LAIR-1 must be the result of a specific combination of stimuli present in cirrhotic patients. This represents an exclusive feature of liver cirrhosis, since blood monocytes from other chronic inflammatory pathologies showed similar or lower LAIR-1 levels compared with those of healthy controls.
Conclusions:
These results may indicate that monocyte LAIR-1 expression is a new biomarker to early detect liver damage caused by chronic inflammation in liver cirrhosis.
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