title: Immune surveillance of mouse brain perivascular spaces by blood-borne macrophages.
abstract: Virchow-Robin's perivascular spaces lie between the basement membrane around pericytes and the basement membrane at the surface of the glia limitans of the brain vessels. They are directly connected to the subpial space and harbour a population of cells distinct from pericytes, perivascular microglia and other cells within perivascular spaces (e.g. T cells and mast cells) in their ability to quickly phagocytose particles from the cerebrospinal fluid (CSF). Morphology, function, and cell surface proteins of these perivascular cells suggest an origin from the monocyte/macrophage lineage. It is currently unclear to what extent these brain perivascular cells represent a resident population of histiocytes or undergo continuous supplementation from blood monocytes. Using transplants of green-fluorescent-protein (GFP)-transfected bone marrow cells, we therefore investigated the replacement of perivascular cells by blood-borne macrophages in adult mice. GFP-positive cells in the perivascular spaces were found as early as 2 weeks post transplantation. The substitution of host perivascular cells by donor-derived macrophages was then evaluated using immunocytochemistry and intraventricular injection of hydrophilic rhodamine-fluorescent tracers. Such tracers diffuse along perivascular spaces and are subsequently phagocytosed by perivascular cells leading to stable phagocytosis-dependent labelling. Thus, the population of newly immigrated macrophages could be related to the total number of perivascular macrophages. This approach revealed a continuous increase of donor-derived perivascular cells. At 14 weeks post transplantation, all perivascular cells were donor-derived. These data show that brain perivascular cells are a population of migratory macrophages and not resident histiocytes.
authors.affiliation: Department of Cell and Neurobiology, Institute of Anatomy, Humboldt-University Hospital Charité, Schumannstrasse 20/21, D-10098 Berlin, Germany. ingo.bechmann@charite.de
authors.forename: I
authors.initials: I
authors.lastname: Bechmann
authors.forename: J
authors.initials: J
authors.lastname: Priller
authors.forename: A
authors.initials: A
authors.lastname: Kovac
authors.forename: M
authors.initials: M
authors.lastname: Böntert
authors.forename: T
authors.initials: T
authors.lastname: Wehner
authors.forename: F F
authors.initials: FF
authors.lastname: Klett
authors.forename: J
authors.initials: J
authors.lastname: Bohsung
authors.forename: M
authors.initials: M
authors.lastname: Stuschke
authors.forename: U
authors.initials: U
authors.lastname: Dirnagl
authors.forename: R
authors.initials: R
authors.lastname: Nitsch
mesh_terms: D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives*; D001808:Blood Vessels / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D016026:Bone Marrow Transplantation; D001921:Brain / Q000098:blood supply / Q000166:cytology* / Q000276:immunology; D002452:Cell Count; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003911:Dextrans; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins; D007107:Immune System / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008264:Macrophages / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020286:Pericytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D010841:Pia Mater / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012235:Rhodamines
chemical_list: D003911:Dextrans; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D012235:Rhodamines; D049452:Green Fluorescent Proteins; C081276:Miniruby; D001710:Biotin