title: Selective localization of bone marrow-derived ramified cells in the brain adjacent to the attachments of choroid plexus.
abstract: Although the immune system modulates higher functions of the brain under non-inflammatory conditions, how immune cells interact with brain parenchymal cells remains to be determined. Using bone marrow chimeric mice in which the recipients' immune system was reconstituted by marrow cells derived from GFP-transgenic mice by syngeneic intra-bone marrow-bone marrow transplantation (IBM-BMT) and by intravenous (IV)-BMT, we examined the distribution, density and differentiation of donor-derived marrow cells in the brain parenchyma 2 weeks and 1, 4 and 8 months after BMT. Marrow-derived cells started to populate discrete brain regions from 1 to 4 months after BMT, exhibited ramified morphology and expressed Iba-1. The ramified marrow-derived cells were distributed in more brain regions and for a longer time after IBM-BMT than IV-BMT. Most of these discrete regions were adjacent to the attachments of choroid plexus that comprised thinned brain parenchyma consisting of astroglial processes in the narrow channel between the ependyma and pia. These specific portions of astroglial processes expressed fractalkine. In the choroid plexus stroma, not only Iba-1+ myeloid cells but also non-myeloid CXCL12-expressing cells were of bone marrow-origin. Transcripts of fractalkine, CXCL12 and their related molecules such as CX3CR1, ADAM10 and CXCR4 were detected in the tissue consisting of the choroid plexus, the attachments and adjacent brain parenchyma. Thus, bone marrow cells selectively enter the discrete brain regions adjacent to the attachments of choroid plexus and differentiate into ramified myeloid cells. Fractalkine in the attachments of choroid plexus and CXCL12 in the choroid plexus stroma may be involved in these brain-immune interactions.
authors.affiliation: Department of Pathology, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kamiya-cho, Kasugai, Aichi 480-0392, Japan; Japan Society for the Promotion of Science, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Hasegawa-Ishii
authors.affiliation: Department of Pathology, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kamiya-cho, Kasugai, Aichi 480-0392, Japan; Department of Pathology, Laboratory Medicine and Radiologic Technology, Central Hospital, Aichi Human Service Center, 713-8 Kamiya-cho, Kasugai, Aichi 480-0392, Japan. Electronic address: ats7@inst-hsc.jp.
authors.forename: Atsuyoshi
authors.initials: A
authors.lastname: Shimada
authors.affiliation: First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8506, Japan.
authors.forename: Muneo
authors.initials: M
authors.lastname: Inaba
authors.affiliation: Department of Stem Cell Disorders, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8506, Japan.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Stem Cell Disorders, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8506, Japan.
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Pathology, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kamiya-cho, Kasugai, Aichi 480-0392, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kawamura
authors.affiliation: Department of Pathology, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kamiya-cho, Kasugai, Aichi 480-0392, Japan; Faculty of Nutrition, Koshien University, 10-1 Momijigaoka, Takarazuka, Hyogo 665-0006, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Takei
authors.affiliation: Department of Pathology, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kamiya-cho, Kasugai, Aichi 480-0392, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Chiba
authors.affiliation: Department of Pathology, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kamiya-cho, Kasugai, Aichi 480-0392, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Hosokawa
authors.affiliation: Department of Stem Cell Disorders, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8506, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000276:immunology; D001921:Brain / Q000166:cytology*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D002454:Cell Differentiation; D002469:Cell Separation; D054428:Chemokine CX3CL1 / Q000096:biosynthesis / Q000235:genetics; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D002831:Choroid Plexus / Q000166:cytology*; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D008297:Male; D008578:Meninges / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000096:biosynthesis; D022423:Myeloid Cells / Q000502:physiology; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D054428:Chemokine CX3CL1; D054377:Chemokine CXCL12; D008840:Microfilament Proteins; D049452:Green Fluorescent Proteins; D012313:RNA