title: Chemokine monocyte chemoattractant protein-1 is expressed by astrocytes after mechanical injury to the brain.
abstract: By 24 h after mechanical trauma to the cerebral cortex, astroglial reaction begins and injury sites are infiltrated by activated mononuclear phagocytes derived from blood-borne monocytes and endogenous microglia. There is little information about cellular interactions between astrocytes and leukocytes during this process. We previously showed that murine astrocytes produce chemokines including monocyte chemoattractant protein-1 (MCP-1) during experimental autoimmune encephalomyelitis. In this study, we asked whether astrocytes produce MCP-1 in the absence of immune mediated inflammation. To address this question, we analyzed the time course and cellular source of MCP-1 in mouse brain after penetrating mechanical injury, with particular focus on early time points before histologic detection of infiltrating mononuclear phagocytes. We observed sharply increased steady state levels of MCP-1 mRNA within 3 h after nitrocellulose membrane stab or implant injury to the adult mouse brain, and MCP-1 protein elevations were documented at 12 h postinjury. In situ hybridization combined with immunohistochemistry for the glial fibrillary acidic protein astrocyte marker showed that astrocytes were the cellular source of MCP-1 mRNA at these early time points after mechanical brain injury. Stab injury to the neonatal brain evoked neither MCP-1 expression nor astrogliosis. These results demonstrate that chemokine gene expression comprises one component of the astrocyte activation program. The data are consistent with a role for MCP-1 in the central nervous system inflammatory response to trauma.
authors.affiliation: Department of Neurosciences, Cleveland Clinic Foundation, OH 44195, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Glabinski
authors.forename: V
authors.initials: V
authors.lastname: Balasingam
authors.forename: M
authors.initials: M
authors.lastname: Tani
authors.forename: S L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: R M
authors.initials: RM
authors.lastname: Strieter
authors.forename: V W
authors.initials: VW
authors.lastname: Yong
authors.forename: R M
authors.initials: RM
authors.lastname: Ransohoff
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000276:immunology* / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000378:metabolism; D001930:Brain Injuries / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014950:Wounds, Penetrating / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D012333:RNA, Messenger