title: Differential and time-dependent expression of monocyte chemoattractant protein-1 mRNA by astrocytes and macrophages in rat brain: effects of ischemia and peripheral lipopolysaccharide administration.
abstract: Increasing evidence indicates a key role of chemoattractant cytokines in the accumulation of leukocytes in the central nervous system (CNS) during the course of inflammatory processes. Monocyte chemoattractant protein (MCP-1/JE), a member of the beta-chemokine (C-C chemokine) family, functions as a potent chemoattractant and activator for monocytes. We have investigated the induction of MCP-1 mRNA using in situ hybridization histochemistry (ISH) and characterized its cellular source by combination of ISH and immunocytochemistry in ischemic rat brains as well as in brains of endotoxin-treated rats. Our results show that 6 h-2 d after middle cerebral artery occlusion (MCAO), MCP-1 mRNA is present in astrocytes surrounding the ischemic tissue (penumbra). At later time points (after 4 d), MCP-1 mRNA is found in macrophages and reactive microglia in the infarcted tissue. Peripheral administration of the bacterial lipopolysaccharide (LPS) induced MCP-1 mRNA throughout the brain in a time-dependent manner (1 h-1 d, peak of expression 6-8 h) and was found in astrocytes. In summary, we have found expression of MCP-1 in (a) astrocytes and to a lesser extent in macrophages/reactive microglia after MCA-occlusion and in (b) astrocytes after peripheral administration of LPS. These findings support that MCP-1 is involved in the CNS response to acute trauma or infection and thus may play a key role in inflammatory processes of the brain.
authors.affiliation: Sandoz Pharma Ltd., Preclinical Research, Basel, Switzerland.
authors.forename: N G
authors.initials: NG
authors.lastname: Gourmala
authors.forename: M
authors.initials: M
authors.lastname: Buttini
authors.forename: S
authors.initials: S
authors.lastname: Limonta
authors.forename: A
authors.initials: A
authors.lastname: Sauter
authors.forename: H W
authors.initials: HW
authors.lastname: Boddeke
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D012333:RNA, Messenger