Amyloid-β induces chemokine secretion and monocyte migration across a human blood-brain barrier model

Milan Fiala, Ling Zhang, Xiaohu Gan, Barbara Sherry, Dennis Taub, Michael C. Graves, Suzan Hama, Dennis Way, Martin Weinand, Marlys Witte, Diane Lorton, Yu-Min Kuo, Alex E. Roher

Research output: Contribution to journalArticle

179 Citations (Scopus)

Abstract

Background: Aside from numerous parenchymal and vascular deposits of amyloid β (Aβ) 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 Aβ 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 Aβ 1-42 on the brain side of the blood-brain barrier model. Results: In cultures of peripheral monocytes, Aβ 1-42 induced the secretion of proinflammatory cytokines TNF-a, IL-6, IL-1β, and IL-12, as well as CC chemokines MCP-1, MIP-1α, and MIP-1β, and CXC chemokine IL-8 in a dose- related fashion. In the blood-brain barrier model, Aβ 1-42 and monocytes on the brain side potentiated monocyte transmigration from the blood side to the brain side. Aβ 1-42 stimulated differentiation of monocytes into adherent macrophages in a dose-related fashion. The magnitude of these proinflammatory effects of Aβ 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.

Original languageEnglish
Pages (from-to)480-489
Number of pages10
JournalMolecular Medicine
Volume4
Issue number7
Publication statusPublished - 1998 Sep 22

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Blood-Brain Barrier
Chemokines
Amyloid
Monocytes
Macrophages
Brain
Alzheimer Disease
Aptitude
Cytokines
CXC Chemokines
CC Chemokines
Neurofibrillary Tangles
Amyloid Plaques
Microglia
Chemotaxis
Interleukin-12
Interleukin-8
Interleukin-1
Blood Vessels
Permeability

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Fiala, M., Zhang, L., Gan, X., Sherry, B., Taub, D., Graves, M. C., ... Roher, A. E. (1998). Amyloid-β induces chemokine secretion and monocyte migration across a human blood-brain barrier model. Molecular Medicine, 4(7), 480-489.
Fiala, Milan ; Zhang, Ling ; Gan, Xiaohu ; Sherry, Barbara ; Taub, Dennis ; Graves, Michael C. ; Hama, Suzan ; Way, Dennis ; Weinand, Martin ; Witte, Marlys ; Lorton, Diane ; Kuo, Yu-Min ; Roher, Alex E. / Amyloid-β induces chemokine secretion and monocyte migration across a human blood-brain barrier model. In: Molecular Medicine. 1998 ; Vol. 4, No. 7. pp. 480-489.
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abstract = "Background: Aside from numerous parenchymal and vascular deposits of amyloid β (Aβ) 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 Aβ 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 Aβ 1-42 on the brain side of the blood-brain barrier model. Results: In cultures of peripheral monocytes, Aβ 1-42 induced the secretion of proinflammatory cytokines TNF-a, IL-6, IL-1β, and IL-12, as well as CC chemokines MCP-1, MIP-1α, and MIP-1β, and CXC chemokine IL-8 in a dose- related fashion. In the blood-brain barrier model, Aβ 1-42 and monocytes on the brain side potentiated monocyte transmigration from the blood side to the brain side. Aβ 1-42 stimulated differentiation of monocytes into adherent macrophages in a dose-related fashion. The magnitude of these proinflammatory effects of Aβ 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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Fiala, M, Zhang, L, Gan, X, Sherry, B, Taub, D, Graves, MC, Hama, S, Way, D, Weinand, M, Witte, M, Lorton, D, Kuo, Y-M & Roher, AE 1998, 'Amyloid-β induces chemokine secretion and monocyte migration across a human blood-brain barrier model', Molecular Medicine, vol. 4, no. 7, pp. 480-489.

Amyloid-β induces chemokine secretion and monocyte migration across a human blood-brain barrier model. / Fiala, Milan; Zhang, Ling; Gan, Xiaohu; Sherry, Barbara; Taub, Dennis; Graves, Michael C.; Hama, Suzan; Way, Dennis; Weinand, Martin; Witte, Marlys; Lorton, Diane; Kuo, Yu-Min; Roher, Alex E.

In: Molecular Medicine, Vol. 4, No. 7, 22.09.1998, p. 480-489.

Research output: Contribution to journalArticle

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T1 - Amyloid-β induces chemokine secretion and monocyte migration across a human blood-brain barrier model

AU - Fiala, Milan

AU - Zhang, Ling

AU - Gan, Xiaohu

AU - Sherry, Barbara

AU - Taub, Dennis

AU - Graves, Michael C.

AU - Hama, Suzan

AU - Way, Dennis

AU - Weinand, Martin

AU - Witte, Marlys

AU - Lorton, Diane

AU - Kuo, Yu-Min

AU - Roher, Alex E.

PY - 1998/9/22

Y1 - 1998/9/22

N2 - Background: Aside from numerous parenchymal and vascular deposits of amyloid β (Aβ) 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 Aβ 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 Aβ 1-42 on the brain side of the blood-brain barrier model. Results: In cultures of peripheral monocytes, Aβ 1-42 induced the secretion of proinflammatory cytokines TNF-a, IL-6, IL-1β, and IL-12, as well as CC chemokines MCP-1, MIP-1α, and MIP-1β, and CXC chemokine IL-8 in a dose- related fashion. In the blood-brain barrier model, Aβ 1-42 and monocytes on the brain side potentiated monocyte transmigration from the blood side to the brain side. Aβ 1-42 stimulated differentiation of monocytes into adherent macrophages in a dose-related fashion. The magnitude of these proinflammatory effects of Aβ 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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Fiala M, Zhang L, Gan X, Sherry B, Taub D, Graves MC et al. Amyloid-β induces chemokine secretion and monocyte migration across a human blood-brain barrier model. Molecular Medicine. 1998 Sep 22;4(7):480-489.