title: Mannose receptor expression specifically reveals perivascular macrophages in normal, injured, and diseased mouse brain.
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.
authors.affiliation: CNS Inflammation Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK. i.galea@soton.ac.uk
authors.forename: Ian
authors.initials: I
authors.lastname: Galea
authors.forename: Karine
authors.initials: K
authors.lastname: Palin
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Newman
authors.forename: Nico
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: V Hugh
authors.initials: VH
authors.lastname: Perry
authors.forename: Delphine
authors.initials: D
authors.lastname: Boche
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D037181:Lectins, C-Type / Q000032:analysis / Q000096:biosynthesis*; D008264:Macrophages / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000032:analysis / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface