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Updated: Aug 21, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Mannose receptor expression specifically reveals perivascular macrophages in normal, injured, and diseased mouse
Ian Galea1, Karine Palin, Tracey A Newman
1CNS Inflammation Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK. i.galea@soton.ac.uk
Abstract:
Perivascular macrophages are believed to have a significant role in inflammation in the central nervous system (CNS). They express a number of different receptors that point toward functions in both innate immunity, through pathogen-associated molecular pattern recognition, phagocytosis, and cytokine responsiveness, and acquired immunity, through antigen presentation and co-stimulation. We are interested in the receptors that are differentially expressed by perivascular macrophages and microglia in both the normal CNS as well as in neuroinflammation and neurodegeneration. In this article we report the use of a well-characterized monoclonal antibody, 5D3, to localize the expression of the mannose receptor to perivascular macrophages in the normal CNS and in various models of brain pathology. Mannose receptor expression was limited to perivascular, meningeal, and choroid plexus macrophages in normal, inflamed, injured, and diseased CNS. In particular, activated microglia and invading hematogenous leukocytes were mannose receptor negative while expressing the F4/80 antigen, macrosialin (CD68), FcRII (CD32), scavenger receptor (CD204), and CR3 (CD11b/CD18). Since the perivascular macrophages expressing the mannose receptor are known to be the only constitutively phagocytic cells in the normal CNS, we injected clodronate-loaded liposomes intracerebroventricularly in control mice to deplete these cells. In these mice, there was no detectable mannose receptor expression in perivascular spaces after immunocytochemistry with the 5D3 monoclonal antibody. This finding underlines the value of the monoclonal antibody 5D3 as a tool to study murine perivascular macrophages selectively. Mannose receptor expression by macrophages located at blood-brain (perivascular), brain-cerebrospinal fluid (CSF) (meningeal), and CSF-blood (choroid plexus) interfaces supports a functional role of these cells in responding to external stimuli such as infection.
Insights
Perivascular macrophages in the central nervous system (CNS) express the mannose receptor. The 5D3 antibody selectively identifies these cells, crucial for immune responses at CNS barriers.
Area of Science:
- Neuroimmunology
- Cell Biology
- Immunology
Background:
- Perivascular macrophages play a key role in central nervous system (CNS) inflammation.
- These macrophages possess receptors involved in both innate and acquired immunity.
- Understanding differential receptor expression between perivascular macrophages and microglia is crucial for CNS research.
Purpose of the Study:
- To investigate the differential expression of receptors by perivascular macrophages and microglia in the CNS.
- To utilize the monoclonal antibody 5D3 to localize mannose receptor expression.
- To explore the role of mannose receptor-expressing perivascular macrophages in CNS pathology.
Main Methods:
- Localization of mannose receptor expression using the 5D3 monoclonal antibody in normal and pathological CNS models.
- Immunocytochemistry to assess macrophage marker expression (F4/80, CD68, CD32, CD204, CD11b/CD18).
- Depletion of perivascular macrophages using clodronate-loaded liposomes in mice.
Main Results:
- Mannose receptor expression was exclusively found in perivascular, meningeal, and choroid plexus macrophages across various CNS conditions.
- Activated microglia and infiltrating leukocytes were negative for mannose receptor but expressed other macrophage markers.
- Depletion of perivascular macrophages eliminated detectable mannose receptor expression in the perivascular space.
Conclusions:
- The monoclonal antibody 5D3 is a valuable tool for selectively studying murine perivascular macrophages.
- Mannose receptor expression identifies macrophages at CNS interfaces (blood-brain, brain-CSF, CSF-blood).
- These macrophages likely play a significant role in responding to external stimuli and maintaining CNS homeostasis.
