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Presence of dendritic cells, MCP‐1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue
Author(s) -
Henkel Jenny S.,
Engelhardt Joseph I.,
Siklós László,
Simpson Ericka P.,
Kim Seung H.,
Pan Tianhong,
Goodman J. Clay,
Siddique Teepu,
Beers David R.,
Appel Stanley H.
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10805
Subject(s) - amyotrophic lateral sclerosis , microglia , dendritic cell , biology , chemokine , cd14 , immune system , spinal cord , motor neuron , cd68 , cd40 , pathology , immunology , medicine , inflammation , immunohistochemistry , neuroscience , cytotoxic t cell , biochemistry , disease , in vitro
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 ALS (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.