Regulation of microglial expression of integrins by poly(ADP-ribose) polymerase-1.
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-kappaB-protein complex. Downregulation of PARP or CD11a by transfection with antisense DNA abrogated microglial migration almost completely and prevented neurons from secondary damage.
Ullrich
O
O
Department of Cell- and Neurobiology, Institute of Anatomy. Medical Faculty (Charité), Humboldt-University Berlin, Schumannstrasse 20/21, 10098 Berlin, Germany. oliver.ullrich@charite.de
Diestel
A
A
Eyüpoglu
I Y
IY
Nitsch
R
R
D000818:Animals; D001927:Brain Diseases / Q000503:physiopathology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D016373:DNA, Antisense; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D009410:Nerve Degeneration / Q000503:physiopathology; D009498:Neurotoxins / Q000494:pharmacology; D010587:Phagocytosis / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D014162:Transfection
D016373:DNA, Antisense; D018690:Excitatory Amino Acid Agonists; D016169:Lymphocyte Function-Associated Antigen-1; D016328:NF-kappa B; D009498:Neurotoxins; D012333:RNA, Messenger; D016202:N-Methylaspartate; D011065:Poly(ADP-ribose) Polymerases