Peripheral monocytes are functionally altered and invade the CNS in ALS patients.
Acta Neuropathol
; 132(3): 391-411, 2016 09.
Article
en En
| MEDLINE
| ID: mdl-26910103
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease affecting primarily the upper and lower motor neurons. A common feature of all ALS cases is a well-characterized neuroinflammatory reaction within the central nervous system (CNS). However, much less is known about the role of the peripheral immune system and its interplay with CNS resident immune cells in motor neuron degeneration. Here, we characterized peripheral monocytes in both temporal and spatial dimensions of ALS pathogenesis. We found the circulating monocytes to be deregulated in ALS regarding subtype constitution, function and gene expression. Moreover, we show that CNS infiltration of peripheral monocytes correlates with improved motor neuron survival in a genetic ALS mouse model. Furthermore, application of human immunoglobulins or fusion proteins containing only the human Fc, but not the Fab antibody fragment, increased CNS invasion of peripheral monocytes and delayed the disease onset. Our results underline the importance of peripheral monocytes in ALS pathogenesis and are in agreement with a protective role of monocytes in the early phase of the disease. The possibility to boost this beneficial function of peripheral monocytes by application of human immunoglobulins should be evaluated in clinical trials.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sistema Mononuclear Fagocítico
/
Médula Espinal
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Leucocitos Mononucleares
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Monocitos
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Sistema Nervioso Central
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Esclerosis Amiotrófica Lateral
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Neuronas Motoras
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Acta Neuropathol
Año:
2016
Tipo del documento:
Article
País de afiliación:
Alemania