Open AccessDifferential Expression of the Chemokine Receptors CX 3 CR1 and CCR1 by Microglia and Macrophages in Myelin‐Oligodendrocyte‐Glycoprotein‐Induced Experimental Autoimmune Encephalomyelitis
Author(s) -
Sunnemark Dan,
Eltayeb Sana,
Wallström Erik,
Appelsved Lena,
Malmberg Åsa,
Lassmann Hans,
EricssonDahlstrand Anders,
Piehl Fredrik,
Olsson Tomas
Publication year - 2003
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2003.tb00490.x
Subject(s) - ccr1 , myelin oligodendrocyte glycoprotein , cx3cr1 , experimental autoimmune encephalomyelitis , chemokine , chemokine receptor , biology , cc chemokine receptors , microglia , microbiology and biotechnology , ccr2 , ccl5 , immunology , cx3cl1 , inflammation , t cell , immune system , il 2 receptor
Chemokines are important for the recruitment of immune cells into sites of inflammation. To better understand their functional roles during inflammation we have here studied the in vivo expression of receptors for the chemokines CCL3/CCL5/CCL7 (MIP‐1α/RANTES/MCP‐3) and CX 3 CL1 (fractalkine), CCR1 and CX 3 CR1, respectively, in rat myelin oligodendrocyte glycoprotein‐induced experimental autoimmune encephalomyelitis. Combined in situ hybridization and immunohistochemistry demonstrated intensely upregulated CCR1 mRN A expression in early, actively demyelinating plaques, whereas CX 3 CR1 displayed a more generalized expression pattern. CX 3 CR1 mRNA expressing cells were identified as microglia on the basis of their cellular morphology and positive GSA/B4 lectin staining. In contrast, CCR1 mRNA was preferentially expressed by ED1 + GSA/B4 + macrophages. The notion of differential chemokine receptor expression in microglia and monocyte‐derived macrophages was corroborated at the protein level by extraction and flow cytometric sorting of cells infiltrating the spinal cord using gating for the surface markers CD45, ED‐2 and CD11b. These observations suggest a differential receptor expression between microglia and monocyte‐derived macrophages and that mainly the latter cell type is responsible for active demyelination. This has great relevance for the possibility of therapeutic intervention in demyelinating diseases such as multiple sclerosis, for example by targeting signaling events leading to monocyte recruitment.