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Differential chemokine receptor expression and function in human monocyte subpopulations
C Weber1, K U Belge, P von Hundelshausen
1Institute for Prevention of Cardiovascular Disease, Ludwig-Maximilians-University, München, Germany. christian.weber@klp.med.uni-muenchen.de
Journal of Leukocyte Biology
|May 16, 2000
Summary
Human monocytes with CD14+CD16+ markers show distinct chemokine receptor profiles, impacting their inflammatory response and tissue localization. These findings are crucial for understanding monocyte behavior in inflammation and infection.
Area of Science:
- Immunology
- Cell Biology
Background:
- Human blood monocytes comprise distinct subsets with varying functions.
- The CD14+CD16+ monocyte subset resembles tissue macrophages and expands during inflammation.
- Chemokine receptors (CCR) are critical for monocyte trafficking and inflammatory responses.
Purpose of the Study:
- To analyze and compare the expression of CC chemokine receptors (CCR) in CD14+CD16+ and CD14++ monocyte subsets.
- To investigate the functional implications of differential CCR expression on monocyte chemotaxis and activation.
Main Methods:
- Multicolor flow cytometry of whole peripheral blood and isolated human monocytes.
- Reverse transcriptase-polymerase chain reaction (RT-PCR) on sorted monocyte subsets.
- Transendothelial chemotaxis assays using monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP-1alpha).
Main Results:
- CD14+CD16+ monocytes exhibited significantly higher CCR5 surface and mRNA expression compared to CD14++ monocytes.
- CD14+CD16+ monocytes showed markedly lower CCR2 surface and mRNA expression than CD14++ monocytes.
- CD14+CD16+ cells demonstrated reduced migration towards MCP-1, indicating functional CCR2 deficiency.
- MCP-1 and MIP-1alpha differentially upregulated CD11b expression in CD14++ and CD14+CD16+ monocytes, respectively.
Conclusions:
- Distinct CCR expression profiles (high CCR5, low CCR2) define the CD14+CD16+ monocyte subset.
- These differences in chemokine receptor expression dictate differential chemotactic responsiveness and functional activation.
- The characteristics of CD14+CD16+ monocytes suggest preactivation and influence their localization in inflammatory conditions and susceptibility to infection.