Amyloid-beta induces chemokine secretion and monocyte migration across a human blood--brain barrier model - PubMed (original) (raw)

L Zhang, X Gan, B Sherry, D Taub, M C Graves, S Hama, D Way, M Weinand, M Witte, D Lorton, Y M Kuo, A E Roher

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

M Fiala et al. Mol Med. 1998 Jul.

Abstract

Background: Aside from numerous parenchymal and vascular deposits of amyloid beta (A beta) 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 A beta 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 beta 1-42 on the brain side of the blood-brain barrier model.

Results: In cultures of peripheral monocytes, A beta 1-42 induced the secretion of proinflammatory cytokines TNF-alpha, IL-6, IL-1 beta, and IL-12, as well as CC chemokines MCP-1, MIP-1 alpha, and MIP-1 beta, and CXC chemokine IL-8 in a dose-related fashion. In the blood-brain barrier model, A beta 1-42 and monocytes on the brain side potentiated monocyte transmigration from the blood side to the brain side. A beta 1-42 stimulated differentiation of monocytes into adherent macrophages in a dose-related fashion. The magnitude of these proinflammatory effects of A beta 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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References

    1. Biochem Biophys Res Commun. 1984 May 16;120(3):885-90 - PubMed
    1. Acta Neuropathol. 1979 Nov;48(2):153-6 - PubMed
    1. J Lipid Res. 1988 Sep;29(9):1243-7 - PubMed
    1. Acta Neuropathol. 1989;77(6):569-75 - PubMed
    1. Can J Neurol Sci. 1989 Nov;16(4 Suppl):535-42 - PubMed

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