Transformation of bone marrow-derived macrophages into ramified microglia during autoimmune inflammation of the axotomized rat facial nucleus

Fluegel, A; Gw, Kreutzberg; Graeber, Manuel B.

doi:10.1016/s0165-5728(98)91342-x

Cited by 2 publications

(2 citation statements)

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“…Under normal circumstances, the brain parenchyma is separated from the circulation by a selective and efficient blood-brain barrier (BBB). Nevertheless, circulating monocytes could traverse the BBB if attracted by powerful chemotactic stimuli, as occurs in some experimental inflammatory states of the brain (10,11) or following intraparenchymal injections of chemokines (12). A breached BBB may also occur as a complication of hypoxic and ischemic episodes resulting from infarctions commonly observed in AD brains (13).…”

Section: Introductionmentioning

confidence: 99%

Amyloid-β Induces Chemokine Secretion and Monocyte Migration across a Human Blood-Brain Barrier Model

Fiala¹,

Zhang²,

Gan³

et al. 1998

Mol Med

204

161

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Background: Aside from numerous parenchymal and vascular deposits of amyloid ((AO) peptide, neurofibrillary tangles, and neuronal and synaptic loss, the neuropathology of Alzheimer's disease is accompanied by a subtle and chronic inflammatory reaction that manifests itself as microglial activation. However, in Alzheimer's disease, alterations in the permeability of the blood-brain barrier and chemotaxis, in part mediated by chemokines and cytokines, may permit the recruitment and transendothelial passage of peripheral cells into the brain parenchyma. Materials and Methods: Human monocytes from different donors were tested for their capacity to differentiate into macrophages and their ability to secrete cytokines and chemokines in the presence of AO3 1-42. A paradigm of the blood-brain barrier was constructed utilizing human brain endothelial and astroglial cells with the anatomical and physiological characteristics observed in vivo. This model was used to test the ability of monocytes/macrophages to transmigrate when challenged by A,B 1-42 on the brain side of the blood-brain barrier model. Results: In cultures of peripheral monocytes, AP3 1-42 induced the secretion of proinflammatory cytokines TNF-a, IL-6, IL-1(3, and IL-12, as well as CC chemokines MCP-1, MIP-la, and MIP-1,B3, and CXC chemokine IL-8 in a doserelated fashion. In the blood-brain barrier model, AP3 1-42 and monocytes on the brain side potentiated monocyte transmigration from the blood side to the brain side. AP3 1-42 stimulated differentiation of monocytes into adherent macrophages in a dose-related fashion. The magnitude of these proinflammatory effects of AP3 1-42 varied dramatically with monocytes from different donors. Conclusion: In some individuals, circulating monocytes/macrophages, when recruited by chemokines produced by activated microglia and macrophages, could add to the inflammatory destruction of the brain in Alzheimer's disease.

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Section: Introductionmentioning

confidence: 99%

Amyloid-β Induces Chemokine Secretion and Monocyte Migration across a Human Blood-Brain Barrier Model

Fiala¹,

Zhang²,

Gan³

et al. 1998

Mol Med

204

161

View full text Add to dashboard Cite

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“…This finding has been widely reproduced in the meantime and microglia research has yielded much information on the molecular characteristics of these cells. In 1998 we also demonstrated that bone marrow-derived precursors can give rise to typical ramified parenchymal microglia in the adult [7, 8], a concept now adopted by others [9]. These observations are of great relevance in the context of our plan to send genetically enhanced microglia as therapeutic agents into diseased brains.…”

Section: The Presence Of Microglia and Related Cells Within Diffuse Gmentioning

confidence: 83%

The Potential for Genetically Altered Microglia to Influence Glioma Treatment

Holsinger²,

Kruse³

et al. 2013

CNSNDDT

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Diffuse and unstoppable infiltration of brain and spinal cord tissue by neoplastic glial cells is the single most important therapeutic problem posed by the common glioma group of tumors: astrocytoma, oligoastrocytoma, oligodendroglioma, their malignant variants and glioblastoma. These neoplasms account for more than two thirds of all malignant central nervous system tumors. However, most glioma research focuses on an examination of the tumor cells rather than on host-specific, tumor micro-environmental cells and factors. This can explain why existing diffuse glioma therapies fail and why these tumors have remained incurable. Thus, there is a great need for innovation. We describe a novel strategy for the development of a more effective treatment of diffuse glioma. Our approach centers on gaining control over the behavior of the microglia, the defense cells of the CNS, which are manipulated by malignant glioma and support its growth. Armoring microglia against the influences from glioma is one of our research goals. We further discuss how microglia precursors may be genetically enhanced to track down infiltrating glioma cells.

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Transformation of bone marrow-derived macrophages into ramified microglia during autoimmune inflammation of the axotomized rat facial nucleus

Cited by 2 publications

References 0 publications

Amyloid-β Induces Chemokine Secretion and Monocyte Migration across a Human Blood-Brain Barrier Model

Amyloid-β Induces Chemokine Secretion and Monocyte Migration across a Human Blood-Brain Barrier Model

The Potential for Genetically Altered Microglia to Influence Glioma Treatment

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