The role of CC chemokine receptor 2 on microglia activation and blood-borne cell recruitment after transient focal cerebral ischemia in mice.
The chemokine receptor 2 (CCR2) is involved in inflammatory reactions following cerebral ischemia. Monocyte chemoattractant protein-1 (MCP-1) binds with high affinity to CCR2. MCP-1 is necessary for recruiting blood-borne cells to the injury site whereas it does not affect microglia activation and migration. MCP-1-deficient mice develop smaller infarcts and show a better functional outcome. CCR2-deficient mice also develop smaller infarcts and have a reduced expression of inflammatory cytokines during reperfusion. In the present study we investigated the differential role of inflammatory cells in CCR2-deficient mice, using green fluorescent protein (GFP)-transgenic bone marrow chimeras. After 30 min of transient middle cerebral artery occlusion (MCAO), activation of local microglia was similar in CCR2-deficient animals and their littermate controls over the study period, whereas an influx of GFP-positive cells was diminished in CCR2-deficient mice. Infiltrating macrophages were significantly reduced at day seven in the deficient animals (26.04+/-25.19 cells/mm(2)) compared to control mice (86.83+/-44.41 cells/mm(2), p<0.001). Neutrophils were also significantly reduced in CCR2-deficient mice (83% on day 2, 76% on day 4 and 89% on day 7, p<0.001). A significant reduction of infarct volume in CCR2-deficient animals could not be detected. In this study a clear differentiation of local and blood-borne inflammatory cell reaction after cerebral ischemia could be shown, demonstrating that CCR2-deficiency attenuates hematogenous cell recruitment to the injury site whereas microglia activation and migration is not affected.
Schilling
Matthias
M
Department of Neurology, University Hospital Münster, Albert-Schweitzer-Str. 33, D-48129 Münster, Germany. schillim@uni-muenster.de
Strecker
Jan-Kolja
JK
Ringelstein
E Bernd
EB
Schäbitz
Wolf-Rüdiger
WR
Kiefer
Reinhard
R
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000276:immunology* / Q000503:physiopathology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology*; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology*; D054390:Receptors, CCR2 / Q000276:immunology*; D018183:Transplantation Chimera
C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2