Presence of Dendritic Cells, MCP-1, and Activated Microglia/Macrophages in Amyotrophic Lateral Sclerosis Spinal Cord Tissue

Jenny S. Henkel, Joseph I. Engelhardt, László Siklós, Ericka P. Simpson, Seung H. Kim, Tianhong Pan, J. Clay Goodman, Teepu Siddique, David R. Beers, Stanley H. Appel*

*Corresponding author for this work

Research output: Contribution to journalArticle

365 Scopus citations

Abstract

Dendritic cells are potent antigen-presenting cells that initiate and amplify immune responses. To determine whether dendritic cells participate in inflammatory reactions in amyotrophic lateral sclerosis (ALS), we examined mRNA expression of dendritic cell surface markers in individual sporadic ALS (sALS), familial (fALS), and nonneurological disease control (NNDC) spinal cord tissues using semiquantitative and real-time reverse transcription polymerase chain reaction (RT-PCR). Immature (DEC205, CD1a) and activated/mature (CD83, CD40) dendritic cell transcripts were significantly elevated in ALS tissues. The presence of immature and activated/mature dendritic cells (CD1a + and CD83 +) was confirmed immunohistochemically in ALS ventral horn and corticospinal tracts. Monocytic/macrophage/microglial transcripts (CD14, CD18, SR-A, CD68) were increased in ALS spinal cord, and activated CD68 + cells were demonstrated in close proximity to motor neurons. mRNA expressions of the chemokine MCP-1, which attracts monocytes and myeloid dendritic cells, and of the cytokine macrophage-colony stimulating factor (M-CSF) were increased in ALS tissues. The MCP-1 protein was expressed in glia in ALS but not in control tissues and was increased in the CSF of ALS patients. Those patients who progressed most rapidly expressed significantly more dendritic transcripts than patients who progressed more slowly. These results support the involvement of immune/inflammatory responses in amplifying motor neuron degeneration in ALS.

Original languageEnglish (US)
Pages (from-to)221-235
Number of pages15
JournalAnnals of neurology
Volume55
Issue number2
DOIs
StatePublished - Feb 2004

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Henkel, J. S., Engelhardt, J. I., Siklós, L., Simpson, E. P., Kim, S. H., Pan, T., Goodman, J. C., Siddique, T., Beers, D. R., & Appel, S. H. (2004). Presence of Dendritic Cells, MCP-1, and Activated Microglia/Macrophages in Amyotrophic Lateral Sclerosis Spinal Cord Tissue. Annals of neurology, 55(2), 221-235. https://doi.org/10.1002/ana.10805