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Rodent monocyte-derived macrophages do not express CD163: Comparative analysis using macrophages from living
Yoichi Saito1, Yukio Fujiwara2, Yasuka L Yamaguchi3
1Laboratory of Bioengineering, Faculty of Advanced Science and Technology, Kumamoto University, Kumamoto, Japan.
Background:
CD163 is a scavenger receptor predominantly expressed on the surfaces of macrophages in various mammalian species and is a marker of anti-inflammatory (M2-like) macrophages. High density of CD163-positive tumor-associated macrophages (TAMs) is associated with worse prognosis in various patient tumors. Interestingly, studies on mice have shown that CD163-positive TAMs only infiltrate the margins of tumor tissues, not the center. Based on these observations, we hypothesized that circulating monocyte-derived macrophages (MDMs), which are the origin of most TAMs, do not express CD163 in mice.
Results:
We examined CD163 expression in MDMs, differentiated from healthy animals in vitro, and in normal, pathogenic, and tumorigenic macrophages infiltrating various tumors and organs across multiple species including primates, rodents, cetartiodactylans, and carnivores. We found that MDMs, including TAMs, do not express CD163 in mice. Our findings also suggest that murine CD163-positive macrophages likely originate from a specific subset of resident macrophages, namely fetal liver monocytes/macrophages, as indicated by fetal analysis. Furthermore, we revealed that the CD163-negative expression pattern in MDMs is a trait shared by the rodent clade.
Conclusions:
Rodent MDMs do not express CD163, a phenotype not shared with MDMs of other mammals. Our findings caution against the extrapolation of rodent experimental results to other animal models.
Insights
Rodent monocyte-derived macrophages (MDMs) do not express CD163, unlike in other mammals. This suggests caution when extrapolating mouse study findings to different species, impacting tumor-associated macrophage research.
Area of Science:
- Immunology
- Cell Biology
- Comparative Mammalian Studies
Background:
- CD163 is a scavenger receptor and M2-like macrophage marker.
- High CD163+ TAMs correlate with poor prognosis in cancer patients.
- Murine TAMs are found at tumor margins, not the center, suggesting a unique origin.
Purpose of the Study:
- To investigate CD163 expression in murine monocyte-derived macrophages (MDMs).
- To determine if circulating MDMs are the source of CD163+ TAMs in mice.
- To compare CD163 expression patterns across different mammalian species.
Main Methods:
- In vitro differentiation of MDMs from healthy animals.
- Analysis of CD163 expression in macrophages from various tissues and tumors.
- Comparative analysis across multiple species including primates and rodents.
- Fetal analysis to trace macrophage origins.
Main Results:
- Murine MDMs, including TAMs, consistently lack CD163 expression.
- CD163+ macrophages in mice appear to originate from a distinct resident macrophage subset (fetal liver monocytes/macrophages).
- The CD163-negative MDM phenotype is conserved within the rodent clade.
Conclusions:
- Rodent MDMs exhibit a unique CD163-negative phenotype, differing from other mammals.
- Findings highlight significant species-specific differences in macrophage biology.
- Caution is advised when generalizing findings from rodent models to other mammalian systems, particularly in cancer research.
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