Expression of monocyte chemoattractant protein-1 and other beta-chemokines by resident glia and inflammatory cells in multiple sclerosis lesions.
Beta-chemokines induce the directional migration of monocytes and T lymphocytes and are thus associated with chronic inflammation. Using immunocytochemistry and in situ hybridisation (ISH) techniques, we have examined the expression of the beta-chemokines monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated upon activation, normal T cell expressed and secreted) in post-mortem human brain from multiple sclerosis (MS) cases, at different stages of lesion development. In actively demyelinating MS plaques RANTES expression was restricted to the blood vessel endothelium, perivascular cells and surrounding astrocytes, suggesting a role in the recruitment of inflammatory cells from the circulation. MCP-1 was expressed by astrocytes and macrophages within acute MS lesions, but was restricted to reactive astrocytes in the parenchyma surrounding the lesion. MIP-1alpha was expressed by astrocytes and macrophages within the plaque, while MIP-1beta was expressed by macrophages and microglia within the lesion, and by microglia in surrounding white matter. Glial cells may be stimulated to produce chemokines and continue the local inflammatory response by forming chemotactic gradients to attract T cells and mononuclear phagocytes from the circulation and surrounding tissue.
Simpson
J E
JE
Department of Biomedical Sciences, Sheffield Hallam University, City Campus, South Yorkshire, UK.
Newcombe
J
J
Cuzner
M L
ML
Woodroofe
M N
MN
D000328:Adult; D002490:Central Nervous System / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000032:analysis / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D017403:In Situ Hybridization; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism*; D009457:Neuroglia / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger