The chemokine MCP-1 and the dendritic and myeloid cells it attracts are increased in the mSOD1 mouse model of ALS.
We recently demonstrated increased dendritic cells (potent antigen-presenting cells) and MCP-1 (monocyte, T-cell, and dendritic cell attracting chemokine) levels in ALS spinal cord tissue. Additionally, we presented data suggesting that dendritic cells might be contributing to the pathogenesis. To determine whether MCP-1 and dendritic cells are present in the mSOD1 mouse and how early in the disease process they are involved, we examined mSOD1 and control spinal cord tissue at different ages using real-time RT-PCR and immunohistochemistry. Dendritic cells were present and transcripts elevated in mSOD1 spinal cord beginning at 110 days. MCP-1 mRNA and immunoreactivity were upregulated in mSOD1 neuronal and glial cells as early as 15 days, prior to any evidence of microglial activation. CD68+ cells were present at 39 days of age. Although it is not clear if these responses are protective or injurious, the early increased MCP-1 expression and CD68+ cell presence indicate early preexisting injury.
Henkel
Jenny S
JS
Department of Neurology, Methodist Research Institute, 6560 Fannin St., Suite # 902, Houston, TX 77030, USA.
Beers
David R
DR
Siklós
László
L
Appel
Stanley H
SH
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D018932:Chemokine CCL2 / Q000276:immunology* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D005911:Gliosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018932:Chemokine CCL2; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C491768:Ccl2 protein, mouse; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse