Production of monocyte chemoattractant protein‐1 in amyotrophic lateral sclerosis

Abstract

The presence of activated microglia in the spinal cord of amyotrophic lateral sclerosis (ALS) patients is usually accompanied by inflammatory biochemical changes, but these are largely unexplored. Monocyte chemoattractant protein-1 (MCP-1) is critical for recruitment of inflammatory cells of monocytic lineage after inflammation or injury to the central nervous system. MCP-1 concentrations were measured by an enzyme-linked immunosorbent assay in the cerebrospinal fluid (CSF) and the serum of 27 patients with ALS and 30 patients with noninflammatory neurological diseases. In ALS, circulating MCP-1 levels were significantly increased in the serum and particularly in the CSF. Immunoreactivity for MCP-1 in ALS spinal cord was detected mostly in astrocytes but also in microglia, neurons, and within the vasculature of the cord. Our findings suggest a role for MCP-1 as an important molecular mediator of the injury response in ALS.

Bioplex analysis of plasma cytokines in Alzheimer’s disease and mild cognitive impairment

“…Previous study showed that CXCR3 ligands, IP-10, and MIG were able to activate the ERK1/2 pathway in mouse cortical neurons, suggesting a role in neuronal injury and tangle formation [24]. The IP-10 also could be linked to A␤ deposition, through the activation of microglia to produce inflammatory cytokines, whereas MCP-1 seems to be involved in a common step associated with neurodegenerative disorders such as FTLD and amyotrophic lateral sclerosis [25,26]. Besides CSF studies, MCP-1 levels have been evaluated in serum, but no significant differences were found in AD patients as compared with age-matched controls [6].…”

Motoneuron Transplantation Rescues the Phenotype of SMARD1 (Spinal Muscular Atrophy with Respiratory Distress Type 1)

“…Their primary role is to induce inflammation through the recruitment of leukocytes by their chemotactic activity and to increase the levels of proinflammatory molecules and chemokines; this has been described in detail in tissues from ALS patients (Nguyen et al, 2001). For instance, expression of the chemokine MCP1, which attracts monocytes and myeloid dendritic cells, is increased in humans with ALS and in a mouse model of ALS (Henkel et al, 2004(Henkel et al, , 2006Baron et al, 2005). In ALS, it is unclear whether these signals simply modulate the innate immune response or if they contribute to motoneuron degeneration as well.…”

Chemokine MIP-2/CXCL2, Acting on CXCR2, Induces Motor Neuron Death in Primary Cultures

“…Recent findings suggest that glial cells (astrocytes and microglia) play a role in motor neuron degeneration [5][6][7] . Although contrasting results have been reported as to cytokine levels in the cerebrospinal fluid or plasma of ALS patients, high concentrations of IL-6, TNF and MCP-1 suggest a neuroinflammatory component [8][9][10][11][12][13][14][15][16] . Inflammation has been implicated in the pathogenesis of many neurodegenerative diseases, and the presence of chemokine receptors has been described in the central nervous system (CNS) [for review see, 17] .…”