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Published on: May 31, 2018
The rat macrophage scavenger receptor CD163: expression, regulation and role in inflammatory mediator production
Machteld M J Polfliet1, Babs O Fabriek, Wouter P Daniëls
1Department of Molecular Cell Biology and Immunology, VU Medical Center, 1007 MB Amsterdam, The Netherlands.
Abstract:
The monoclonal antibody ED2 is widely used to define macrophages (mphi) in the rat. We have recently identified the ED2 antigen as the rat CD163 glycoprotein. CD163 is a member of the scavenger receptor cysteine-rich group B (SRCR-B) family and functions as a scavenger receptor for hemoglobin-haptoglobin complexes. Moreover, CD163 has also been indicated as a marker for alternatively activated mphi. In the current study, we identify rat CD163/ED2-antigen as a marker for mature tissue mphi. Rat CD163 is constitutively expressed on most subpopulations of mature tissue mphi, including splenic red pulp mphi, thymic cortical mphi, Kupffer cells in the liver, resident bone marrow mphi and central nervous system perivascular and meningeal mphi, but is apparently absent from monocytes. Rat CD163 expression can be promoted by glucocorticoids, and this can be further enhanced by IL4. Finally, engagement of rat CD163 on peritoneal mphi induces the production of pro-inflammatory mediators, including NO, IL-1beta, IL-6 and TNF-alpha. Collectively, our findings identify rat CD163 as a broadly expressed macrophage scavenger receptor that may play a role in the activation of mphi during hemolytic and/or inflammatory conditions.
Insights
The rat CD163 glycoprotein, also known as ED2 antigen, marks mature tissue macrophages. Its engagement triggers pro-inflammatory mediator release, suggesting a role in inflammation.
Area of Science:
- Immunology
- Cell Biology
Background:
- The monoclonal antibody ED2 is a standard marker for rat macrophages.
- The ED2 antigen has been identified as the rat CD163 glycoprotein, a scavenger receptor involved in hemoglobin-haptoglobin uptake.
- CD163 is also implicated as a marker for alternatively activated macrophages.
Purpose of the Study:
- To identify rat CD163/ED2-antigen as a marker for mature tissue macrophages.
- To investigate the expression patterns and regulation of rat CD163.
- To explore the functional consequences of rat CD163 engagement.
Main Methods:
- Immunohistochemistry and flow cytometry to determine CD163 expression on various rat tissues and cell types.
- Treatment with glucocorticoids and IL-4 to assess their effect on CD163 expression.
- Stimulation of peritoneal macrophages to analyze mediator production upon CD163 engagement.
Main Results:
- Rat CD163 is constitutively expressed on diverse mature tissue macrophage subpopulations, including splenic, thymic, liver (Kupffer cells), bone marrow, and central nervous system macrophages.
- CD163 is notably absent from monocytes.
- Glucocorticoids and IL-4 can promote and enhance CD163 expression, respectively.
- Engagement of CD163 on peritoneal macrophages induces the production of pro-inflammatory mediators such as nitric oxide (NO), IL-1beta, IL-6, and TNF-alpha.
Conclusions:
- Rat CD163/ED2-antigen is a reliable marker for mature tissue macrophages across various organs.
- Rat CD163 functions as a scavenger receptor and its activation can lead to pro-inflammatory responses.
- These findings highlight the potential role of rat CD163 in macrophage activation during hemolytic and inflammatory conditions.
