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Quantifying Human Monocyte Chemotaxis In Vitro and Murine Lymphocyte Trafficking In Vivo
Published on: October 30, 2017
Migratory Response of Human NK Cells to Monocyte-Chemotactic Proteins
1Department of Immunology and Cell Biology, Istituto di Ricerche Farmacologiche "Mario Negri,", Via Eritrea 62, Milan, 20157, Italy
Abstract:
NK cells are present mostly in blood and spleen but under certain pathological and physiological conditions rapidly accumulate at extrahematic sites. The present study investigates the responsiveness of NK cells to C-C chemokines and the mechanisms of emigration from the bloodstream. MCP-1 induced migration across polycarbonate filters of IL-2-activated NK cells, whereas it was a weak attractant for unstimulated cells. The related chemokines MCP-2 and MCP-3 were also active. IL-2-activated NK cells showed specific binding sites for labeled MCP-1, and cell migration was inhibited by both cholera and Bordetella pertussis toxins. In agreement with functional assays the expression of mRNA specific for MCP-1 receptors was detectable only in IL-2-activated NK cells. The ability of NK cells to respond to MCP-1 and related chemokines may be one important determinant of NK cell emigration and recruitment in tissues.
Insights
Natural killer (NK) cells rapidly accumulate at extrahepatic sites. This study shows that C-C chemokines like MCP-1 induce NK cell migration, crucial for tissue recruitment.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Natural killer (NK) cells are immune cells primarily found in blood and spleen.
- Under specific conditions, NK cells can migrate to and accumulate at sites outside the bloodstream (extrahematic sites).
- Understanding the mechanisms of NK cell emigration is vital for controlling their tissue distribution.
Purpose of the Study:
- To investigate the responsiveness of NK cells to C-C chemokines.
- To elucidate the mechanisms underlying NK cell emigration from the bloodstream.
- To determine the role of chemokines in NK cell recruitment to tissues.
Main Methods:
- Investigated NK cell migration across polycarbonate filters using chemokines like MCP-1, MCP-2, and MCP-3.
- Assessed the binding of labeled MCP-1 to IL-2-activated NK cells.
- Utilized cholera toxin and Bordetella pertussis toxin to study signaling pathways involved in migration.
- Analyzed the expression of mRNA for MCP-1 receptors in NK cells.
Main Results:
- Monocyte chemoattractant protein-1 (MCP-1) induced significant migration of IL-2-activated NK cells, but not unstimulated cells.
- Related chemokines MCP-2 and MCP-3 also demonstrated chemoattractant activity.
- IL-2-activated NK cells exhibited specific binding sites for MCP-1.
- Cell migration was inhibited by cholera and Bordetella pertussis toxins, suggesting G protein-coupled receptor involvement.
- mRNA expression for MCP-1 receptors was detected exclusively in IL-2-activated NK cells.
Conclusions:
- NK cell responsiveness to MCP-1 and related chemokines is dependent on activation status (e.g., IL-2 activation).
- These chemokine interactions are likely a key factor in NK cell emigration from blood into tissues.
- The findings provide insights into the molecular mechanisms governing NK cell trafficking and tissue-specific accumulation.
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