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Regulation of microglial expression of integrins by poly(ADP-ribose) polymerase-1

Nature Cell Biology volume 3, pages 1035–1042 (2001)Cite this article

Abstract

Excitotoxic brain lesions initially result in the primary destruction of brain parenchyma, after which microglial cells migrate towards the sites of injury. At these sites, the cells produce large quantities of oxygen radicals and cause secondary damage that accounts for most of the loss of brain function. Here we show that this microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, regulated by the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) through the formation of a nuclear PARP–NF-κB-protein complex. Downregulation of PARP or CD11a by transfection with antisense DNA abrogated microglial migration almost completely and prevented neurons from secondary damage.

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Figure 4: CD11a expression is dependent on NF-κB-translocation and PARP activity.
Figure 1: Downregulation of PARP-1 in BV-2 microglial cells protects from secondary neuronal damage in living OHSCs.
Figure 5: Downregulation of PARP-1 in primary microglial cells inhibits migration towards the sites of neuronal injury and protects from neuronal damage in living OHSCs.
Figure 2: Microglial migration towards the sites of neuronal injury is strongly controlled by PARP-1.
Figure 3: PARP-1 regulates CD11a expression in activated BV-2 microglial cells, which is required for the migration towards the sites of neuronal injury.

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Acknowledgements

This work was supported by a grant from the Deutsche Forschunsgemeinschaft to O.U. (UL177/2-1) and to R.N. (SFB507/C1). We thank T. Irico for careful secretary assistance.

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  1. Oliver Ullrich and Antje Diestel: These authors contributed equally to this work

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  1. Department of Cell- and Neurobiology, Institute of Anatomy. Medical Faculty (Charité), Humboldt-University Berlin, Schumannstrasse 20/21, Berlin, 10098, Germany

    Oliver Ullrich, Antje Diestel, Ilker Y. Eyüpoglu & Robert Nitsch

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Correspondence to Oliver Ullrich.

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Ullrich, O., Diestel, A., Eyüpoglu, I. et al. Regulation of microglial expression of integrins by poly(ADP-ribose) polymerase-1. Nat Cell Biol 3, 1035–1042 (2001). https://doi.org/10.1038/ncb1201-1035

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