Expression of the interferon-gamma-inducible chemokines IP-10 and Mig and their receptor, CXCR3, in multiple sclerosis lesions.
The recruitment of leucocytes to sites of inflammation is an important feature of multiple sclerosis (MS) pathology. Chemokines are involved in the activation and specific directional migration of monocytes and T-lymphocytes to sites of inflammation. Using immunocytochemistry, the expression of the alpha-chemokines, interferon (IFN)-gamma-inducible protein-10 (IP-10) and monokine induced by IFN-gamma (Mig), and their receptor CXCR3 have been examined in post-mortem central nervous system (CNS) tissue from MS cases at different stages of lesion development. In actively demyelinating lesions both IP-10 and Mig protein were predominantly expressed by macrophages within the plaque and by reactive astrocytes in the surrounding parenchyma. CXCR3 was expressed by T cells and by astrocytes within the plaque. Interferon-gamma may stimulate glial cells to express IP-10 and Mig, which continue the local inflammatory response by selectively recruiting activated T-lymphocytes into the CNS.
Simpson
J E
JE
Division of Biomedical Sciences, Sheffield Hallam University, Sheffield, South Yorkshire and Multiple Sclerosis Laboratory, Institute of Neurology, London, UK.
Newcombe
J
J
Cuzner
M L
ML
Woodroofe
M N
MN
D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D002490:Central Nervous System / Q000737:chemistry / Q000276:immunology; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000032:analysis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003711:Demyelinating Diseases / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma