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GM‐CSF promotes migration of human monocytes across the blood brain barrier
Authors:Daphne Y. S. Vogel  Gijs Kooij  Priscilla D. A. M. Heijnen  Marjolein Breur  Laura A. N. Peferoen  Paul van der Valk  Helga E. de Vries  Sandra Amor  Christine D. Dijkstra
Affiliation:1. Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, Neuroscience Campus, Amsterdam, The Netherlands;2. Department of Pathology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands;3. Department of Neuroimmunology Unit, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK
Abstract:Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Infiltration of monocytes into the CNS is crucial for disease onset and progression. Animal studies indicate that granulocyte‐macrophages colony‐stimulating factor (GM‐CSF) may play an essential role in this process, possibly by acting on the migratory capacities of myeloid cells across the blood–brain barrier. This study describes the effect of GM‐CSF on human monocytes, macrophages, and microglia. Furthermore, the expression of GM‐CSF and its receptor was investigated in the CNS under healthy and pathological conditions. We show that GM‐CSF enhances monocyte migration across human blood–brain barrier endothelial cells in vitro. Next, immunohistochemical analysis on human brain tissues revealed that GM‐CSF is highly expressed by microglia and macrophages in MS lesions. The GM‐CSF receptor is expressed by neurons in the rim of combined gray/white matter lesions and astrocytes. Finally, the effect of GM‐CSF on human macrophages was determined, revealing an intermediate activation status, with a phenotype similar to that observed in active MS lesions. Together our data indicate that GM‐CSF is a powerful stimulator of monocyte migration, and is abundantly present in the inflamed CNS where it may act as an activator of macrophages and microglia.
Keywords:CNS  Migration  Monocytes  MS  macrophages
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