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PMID: 12547701 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

CC chemokine receptor 8 in the central nervous system is associated with phagocytic macrophages.

The American journal of pathology ·Vol. 162 ·No. 2 ·2003-02-00 ·Pages 427-38

Trebst C, Staugaitis SM, Kivisäkk P, Mahad D, Cathcart MK, Tucky B, Wei T, Rani MR, Horuk R, Aldape KD, Pardo CA, Lucchinetti CF, Lassmann H, Ransohoff RM

Abstract

CC chemokine receptor 8 (CCR8) has been detected in vitro on type 2 helper and regulatory lymphocytes, which might exert beneficial functions in multiple sclerosis (MS) and on macrophages and microglia, possibly promoting tissue injury in MS lesions. To discriminate the relevant expression pattern in vivo, we defined the cell types that expressed CCR8 in MS lesions and determined the relationship of CCR8 expression and demyelinating activity. CCR8 was not expressed on T cells but was associated with phagocytic macrophages and activated microglia in MS lesions and directly correlated with demyelinating activity. To identify factors associated with CCR8 expression, the study was extended to other central nervous system (CNS) pathologies. CCR8 was consistently expressed on phagocytic macrophages and activated microglia in stroke and progressive multifocal leukoencephalopathy, but not expressed on microglia in pathologies that lacked phagocytic macrophages such as senile change of the Alzheimer's type. CCR8 was up-regulated by macrophage differentiation and activating stimuli in vitro. In summary CNS CCR8 expression was associated with phagocytic macrophages and activated microglial cells in human CNS diseases, suggesting that CCR8 may be a feasible target for therapeutic intervention in MS. CCR8 expression may also indicate a selective program of mononuclear phagocyte gene expression.

MeSH Terms
Adult Autopsy Biopsy Central Nervous System Diseases/immunology,pathology Chemokines, CC/analysis Female Flow Cytometry Humans Immunohistochemistry Macrophages/immunology Male Microglia/immunology Middle Aged Multiple Sclerosis/immunology,pathology Phagocytosis Receptors, CCR8 Receptors, Chemokine/analysis,genetics Reverse Transcriptase Polymerase Chain Reaction Th2 Cells/immunology
Chemicals
CCR8 protein, human Chemokines, CC Receptors, CCR8 Receptors, Chemokine
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Trebst Corinna
Department of Neurosciences, The Lerner Research Institute, Cleveland, Ohio 44195, USA.
Staugaitis Susan M
Kivisäkk Pia
Mahad Don
Cathcart Martha K
Tucky Barbara
Wei Tao
Rani Mysore R Sandhya
Horuk Richard
Aldape Kenneth D
Pardo Carlos A
Lucchinetti Claudia F
Lassmann Hans
Ransohoff Richard M
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)63837-0
Published
2003-02-00
Pages
427-38
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1851139
Subset
IM
Grants
NINDS NIH HHS · P01 NS038667 · United States
NINDS NIH HHS · P01NS 38667 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)63837-0 PMC Full Text View journal details
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