PMID- 16733654
OWN - NLM
STAT- MEDLINE
DCOM- 20070201
LR  - 20071115
IS  - 0001-6322 (Print)
IS  - 0001-6322 (Linking)
VI  - 112
IP  - 2
DP  - 2006 Aug
TI  - Chemokine expression by astrocytes plays a role in microglia/macrophage 
      activation and subsequent neurodegeneration in secondary progressive multiple 
      sclerosis.
PG  - 195-204
AB  - The pathological hallmarks of secondary progressive (SP) multiple sclerosis (MS) 
      include slowly expanding demyelination and axonal damage with less inflammation. 
      To elucidate the pathomechanisms of secondary progressive (SP) multiple sclerosis 
      (MS), we have investigated the expression of chemokines, chemokine receptors, 
      matrix metalloproteinase-9 (MMP-9) and immunoglobulins in the demyelinating 
      plaques. Immunohistochemical analysis revealed that numerous hypertrophic 
      astrocytes were observed at the rim, but not in the center, of the chronic active 
      lesions. Microglia/macrophages phagocytosing myelin debris were also found at the 
      lesion border. In contrast, T cell infiltration was minimal in these plaques. 
      Characteristically, at the rim of the lesions, there were abundant 
      immunoreactivities for monocyte chemoattractant protein-1 (MCP-1)/CCL2 and 
      interferon-gamma inducible protein-10 (IP-10)/CXCL10 and their receptors, CCR2 
      and CXCR3, while these immunoreactivities were weak in the center, thus forming a 
      chemokine gradient. Double immunofluorescense staining demonstrated that cellular 
      sources of MCP-1/CCL2 and IP-10/CXCL10 were hypertrophic astrocytes and that both 
      astrocytes and microglia/macrophages expressed CCR2 and CXCR3. MMP-9 was also 
      present at the rim of the lesions. These results suggest that MCP-1/CCL2 and 
      IP-10/CXCL10 produced by astrocytes may activate astrocytes in an autocrine or 
      paracrine manner and direct reactive gliosis followed by migration and activation 
      of microglia/macrophages as effector cells in demyelinating lesions. Targeting 
      chemokines in SPMS may therefore be a powerful therapeutic approach to inhibit 
      lesional expansion.
FAU - Tanuma, Naoyuki
AU  - Tanuma N
AD  - Department of Molecular Neuropathology, Tokyo Metropolitan Institute for 
      Neuroscience, Fuchu, Tokyo, 183-8526, Japan.
FAU - Sakuma, Hiroshi
AU  - Sakuma H
FAU - Sasaki, Atsushi
AU  - Sasaki A
FAU - Matsumoto, Yoh
AU  - Matsumoto Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060530
PL  - Germany
TA  - Acta Neuropathol
JT  - Acta neuropathologica
JID - 0412041
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (CXCL10 protein, human)
RN  - 0 (CXCR3 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL10)
RN  - 0 (Chemokines)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, CXCR3)
RN  - 0 (Receptors, Chemokine)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Astrocytes/*metabolism/pathology
MH  - Cell Movement
MH  - Chemokine CCL2/genetics/metabolism
MH  - Chemokine CXCL10
MH  - Chemokines/genetics/*metabolism
MH  - Chemokines, CXC/genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation
MH  - Humans
MH  - Macrophage Activation/*physiology
MH  - Male
MH  - Matrix Metalloproteinase 9/genetics/metabolism
MH  - Microglia/*physiology
MH  - Middle Aged
MH  - Multiple Sclerosis, Chronic Progressive/metabolism/pathology/*physiopathology
MH  - Nerve Degeneration/*physiopathology
MH  - Receptors, CCR2
MH  - Receptors, CXCR3
MH  - Receptors, Chemokine/genetics/metabolism
EDAT- 2006/05/31 09:00
MHDA- 2007/02/03 09:00
CRDT- 2006/05/31 09:00
PHST- 2006/03/29 00:00 [received]
PHST- 2006/05/04 00:00 [accepted]
PHST- 2006/05/03 00:00 [revised]
PHST- 2006/05/31 09:00 [pubmed]
PHST- 2007/02/03 09:00 [medline]
PHST- 2006/05/31 09:00 [entrez]
AID - 10.1007/s00401-006-0083-7 [doi]
PST - ppublish
SO  - Acta Neuropathol. 2006 Aug;112(2):195-204. doi: 10.1007/s00401-006-0083-7. Epub 
      2006 May 30.