title: Expression of MCP-1 and fractalkine on endothelial cells and astrocytes may contribute to the invasion and migration of brain macrophages in ischemic rat brain lesions.
abstract: Some macrophages expressing NG2 chondroitin sulfate proteoglycan (NG2) and the macrophage marker Iba1 accumulate in the ischemic core of a rat brain subjected to transient middle cerebral artery occlusion (MCAO) for 90 min. These cells are termed BINCs (for brain Iba1(+) /NG2(+) cells) and may play a neuroprotective role. Because BINCs are bone marrow-derived cells, they are able to invade ischemic tissue after the onset of an ischemic insult. In this study, chemokine-based mechanisms underlying the invasion of BINCs or their progenitor cells were investigated. We found that isolated BINCs expressed mRNA encoding CCR2 and CX3CR1 at high levels. Cultured astrocytes expressed mRNA encoding their ligands, MCP-1 and fractalkine. Recombinant MCP-1 and/or fractalkine, as well as astrocytes, induced the migration of BINCs in vitro. mRNA for MCP-1, fractalkine, CCR2, and CX3CR1 was expressed in the ischemic core during the acute phase of the ischemic event. Immunohistochemical studies revealed that vascular endothelial cells and astrocytic endfeet expressed MCP-1 and fractalkine, respectively, in the ischemic core during the acute phase. CCR2(+) /Iba1(+) monocytes attached to the inside of the vascular wall at 1 day postreperfusion (dpr), and there were CCR2(+) /CX3CR1(+) macrophage-like cells in the parenchyma in the ischemic lesion core at 2 dpr, which may be the progenitors for BINCs. These results suggest that CCR2(+) monocytes are first attracted to the ischemic lesion by MCP-1(+) endothelial cells and migrate toward fractalkine(+) astrocytic endfeet through the disrupted blood-brain barrier. Thus, chemokines may play a critical role in the accumulation of neuroprotective BINCs. © 2013 Wiley Periodicals, Inc.
authors: Department of Neurosurgery, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
authors: Nari
authors: N
authors: Tei
authors: Junya
authors: J
authors: Tanaka
authors: Kana
authors: K
authors: Sugimoto
authors: Tasuku
authors: T
authors: Nishihara
authors: Ryutaro
authors: R
authors: Nishioka
authors: Hisaaki
authors: H
authors: Takahashi
authors: Hajime
authors: H
authors: Yano
authors: Shirabe
authors: S
authors: Matsumoto
authors: Shiro
authors: S
authors: Ohue
authors: Hideaki
authors: H
authors: Watanabe
authors: Yoshiaki
authors: Y
authors: Kumon
authors: Takanori
authors: T
authors: Ohnishi
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D001253:Astrocytes / Q000502:physiology*; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology*; D002545:Brain Ischemia / Q000150:complications; D039481:CD11b Antigen / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D039481:CD11b Antigen; D000073883:CX3C Chemokine Receptor 1; D002135:Calcium-Binding Proteins; D018932:Chemokine CCL2; D054428:Chemokine CX3CL1; D005904:Glial Fibrillary Acidic Protein; D037102:Lectins; D008840:Microfilament Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D000099216:Chondroitin Sulfate Proteoglycan 4; C100745:Aif1 protein, rat; C491766:Ccl2 protein, rat; C515336:Ccr2 protein, rat; C471885:Cx3cr1 protein, mouse