The ectonucleotidase cd39/ENTPDase1 modulates purinergic-mediated microglial migration

被引：85

作者：

Faerber, Katrin ^{[1
]}

Markworth, Soeren ^{[1
]}

Pannasch, Ulrike ^{[1
]}

Nolte, Christiane ^{[1
]}

Prinz, Vincent ^{[2
]}

Kronenberg, Golo ^{[2
,3
]}

Gertz, Karen ^{[2
]}

Endres, Matthias ^{[2
]}

Bechmann, Ingo ^{[4
]}

Enjyoji, Keiichi ^{[5
]}

Robson, Simon C. ^{[5
]}

Kettenmann, Helmut ^{[1
]}

机构：

[1] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany

[2] Charite Univ Med Berlin, Neurol Klin & Poliklin, Berlin, Germany

[3] Free Univ Berlin, Dept Psychiat, D-1000 Berlin, Germany

[4] Goethe Univ Frankfurt, Inst Clin Neuroanat, Frankfurt, Germany

[5] BIDMC, Transplantat Ctr, Boston, MA USA

来源：

GLIA | 2008年 / 56卷 / 03期

关键词：

microglia; purinergic receptors type 2; migration; ATP; cd39; ENTPDase; brain;

D O I：

10.1002/glia.20606

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Microglia is activated by brain injury. They migrate in response to ATP and although adenosine alone has no effect on wild type microglial migration, we show that inhibition of adenosine receptors impedes ATP triggered migration. CD39 is the dominant cellular ectonucleotidase that degrades nucleotides to nucleosides, including adenosine. Importantly, ATP fails to stimulate P2 receptor mediated migration in cd39(-/-) microglia. However, the effects of ATP on migration in cd39(-/-) microglia can be restored by co-stimulation with adenosine or by addition of a soluble ectonucleotidase. We also tested the impact of cd39-deletion in a model of ischemia, in an entorhinal cortex lesion and in the facial nucleus after facial nerve lesion. The accumulation of microglia at the pathological sites was markedly decreased in cd39(-/-) animals. We conclude that the co-stimulation of purinergic and adenosine receptors is a requirement for microglial migration and that the expression of cd39 controls the ATP/adenosine balance. (C) 2007 Wiley-Liss, Inc.

引用

页码：331 / 341

页数：11

共 51 条

[1] Pathophysiological roles of extracellular nucleotides in glial cells: differential expression of purinergic receptors in resting and activated microglia [J].