PMID- 22197827
OWN - NLM
STAT- MEDLINE
DCOM- 20120326
LR  - 20120203
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Linking)
VI  - 233
IP  - 2
DP  - 2012 Feb
TI  - MCP-1/CCR-2-double-deficiency severely impairs the migration of hematogenous 
      inflammatory cells following transient cerebral ischemia in mice.
PG  - 849-58
LID - 10.1016/j.expneurol.2011.12.011 [doi]
AB  - Monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR-2 are known to 
      play a major role in inflammatory responses after cerebral ischemia. Mice 
      deficient in either MCP-1 or CCR-2 have been reported to develop smaller infarct 
      sizes and show decreased numbers of infiltrating inflammatory cells. In the 
      present study we used green fluorescent protein (GFP) transgenic mice to 
      investigate the effect of MCP-1/CCR-2-double deficiency on the recruitment of 
      inflammatory cells in a model of both, mild and severe cerebral ischemia. We show 
      that MCP-1/CCR-2-double deficiency virtually entirely abrogates the recruitment 
      of hematogenous macrophages and significantly reduces neutrophil migration to the 
      ischemic brain 4 and 7 days following focal cerebral ischemia. This argues for a 
      predominant role of the MCP-1/CCR-2 axis in chemotaxis of monocytes despite a 
      wide redundancy in the chemokine-receptor-system. Chemokine analysis revealed 
      that even candidates known to be involved in monocyte and neutrophil recruitment 
      like MIP-1alpha, CXCL-1, C5a, G-CSF and GM-CSF showed a reduced and delayed or even a 
      lack of relevant compensatory response in MCP-1(-/-)/CCR-2(-/-)-mice. Solely, 
      chemokine receptor 5 (CCR-5) increased early in both, but rose above wildtype 
      levels at day 7 in MCP-1(-/-)/CCR-2(-/-)-animals, which might explain the higher 
      number of activated microglial cells compared to control mice. Our study was, 
      however, not powered to investigate infarct volumes. Further studies are needed 
      to clarify whether these mechanisms of inflammatory cell recruitment might be 
      essential for early infarct development and final infarct size and to evaluate 
      potential therapeutic implications.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Schuette-Nuetgen, Katharina
AU  - Schuette-Nuetgen K
AD  - Department of Neurology, University of Munster, Albert-Schweitzer Str. 33, 48129 
      Munster, Germany.
FAU - Strecker, Jan-Kolja
AU  - Strecker JK
FAU - Minnerup, Jens
AU  - Minnerup J
FAU - Ringelstein, E Bernd
AU  - Ringelstein EB
FAU - Schilling, Matthias
AU  - Schilling M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20111216
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Receptors, CCR2)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/*deficiency
MH  - Inflammation/genetics/metabolism/pathology
MH  - Inflammation Mediators/*physiology
MH  - Ischemic Attack, Transient/genetics/*metabolism/*pathology
MH  - Macrophages/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Microglia/metabolism/pathology
MH  - Neutrophil Infiltration/*genetics
MH  - Receptors, CCR2/*deficiency
MH  - Severity of Illness Index
EDAT- 2011/12/27 06:00
MHDA- 2012/03/27 06:00
CRDT- 2011/12/27 06:00
PHST- 2011/07/12 00:00 [received]
PHST- 2011/12/01 00:00 [revised]
PHST- 2011/12/07 00:00 [accepted]
PHST- 2011/12/27 06:00 [entrez]
PHST- 2011/12/27 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
AID - S0014-4886(11)00463-8 [pii]
AID - 10.1016/j.expneurol.2011.12.011 [doi]
PST - ppublish
SO  - Exp Neurol. 2012 Feb;233(2):849-58. doi: 10.1016/j.expneurol.2011.12.011. Epub 
      2011 Dec 16.