Activation of Microglia by Amyloid β Requires P2X7 Receptor Expression

被引：235

作者：

Sanz, Juana M. ^{[2
]}

Chiozzi, Paola ^{[1
,3
]}

Ferrari, Davide ^{[1
,3
]}

Colaianna, Marilena ^{[4
]}

Idzko, Marco ^{[5
]}

Falzoni, Simonetta ^{[1
,3
]}

Fellin, Renato ^{[2
]}

Trabace, Luigia ^{[4
]}

Di Virgilio, Francesco ^{[1
,3
]}

机构：

[1] Univ Ferrara, Dept Expt & Diagnost Med, Sect Gen Pathol, I-44100 Ferrara, Italy

[2] Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med, I-44100 Ferrara, Italy

[3] Univ Ferrara, Interdisciplinary Ctr Study Inflammat, I-44100 Ferrara, Italy

[4] Univ Foggia, Dept Biomed Sci, Foggia, Italy

[5] Univ Hosp, Dept Pulm Med, Freiburg, Germany

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 182卷 / 07期

关键词：

INTERLEUKIN-1-BETA RELEASE; INFLAMMATORY PROCESSES; ALZHEIMER-DISEASE; CELLS; ATP; PROTEIN; MODULATION; BRAIN; PHAGOCYTOSIS; PROGRESSION;

D O I：

10.4049/jimmunol.0803612

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Extracellular ATP is a mediator of intercellular communication and a danger signal. Release of this and other nucleotides modulates microglia responses via P2Y and P2X receptors, among which the P2X(7) subtype stands out for its proinflammatory activity and for up-regulation in a transgenic model of Alzheimer disease and in brains from Alzheimer disease patients. Here we show that amyloid beta (A beta) triggered increases in intracellular Ca2+ ([Ca2+](i)), ATP release, IL-1 beta secretion, and plasma membrane permeabilization in microglia from wild-type but not from P2X(7)-deleted mice. Likewise, intra-hippocampal injection of A beta caused a large accumulation of IL-1 beta in wild-type but not in P2X(7)(-/-) mice. These observations suggest that A beta activates a purinergic autocrine/paracrine stimulatory loop of which the P2X(7) receptor is an obligate component. Identification of the P2X(7) receptor as a non-dispensable factor of A beta-mediated microglia stimulation may open new avenues for the treatment of Alzheimer disease. The Journal of Immunology, 2009, 182: 4378-4385.

引用

页码：4378 / 4385

页数：8

共 55 条

[1] Cytokines and acute neurodegeneration [J].

Allan, SM ;

Rothwell, NJ .

NATURE REVIEWS NEUROSCIENCE, 2001, 2 (10) :734-744

[2] P2X7 receptor activation in rat brain cultured astrocytes increases the biosynthetic release of cysteinyl leukotrienes [J].

Ballerini, P ;

Ciccarelli, R ;

Caciagli, F ;

Rathbone, MP ;

Werstiuk, ES ;

Traversa, U ;

Buccella, S ;

Giuliani, P ;

Jiang, S ;

Nargi, E ;

Visini, D ;

Santavenere, C ;

Di Iorio, P .

INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY, 2005, 18 (03) :417-430

[3] Detection of local ATP release from activated platelets using cell surface-attached firefly luciferase [J].

Beigi, R ;

Kobatake, E ;

Aizawa, M ;

Dubyak, GR .

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1999, 276 (01) :C267-C278

[4] Adenosine 5′-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation [J].

Bours, M. J. L. ;

Swennen, E. L. R. ;

Di Virgilio, F. ;

Cronstein, B. N. ;

Dagnelie, P. C. .

PHARMACOLOGY & THERAPEUTICS, 2006, 112 (02) :358-404

[5] P2Y2 nucleotide receptors enhance α-secretase-dependent amyloid precursor protein processing [J].

Camden, JM ;

Schrader, AM ;

Camden, RE ;

González, FA ;

Erb, L ;

Seye, CI ;

Weisman, GA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (19) :18696-18702

[6] Activation of toll-like receptor 2 on microglia promotes cell uptake of Alzheimer disease-associated amyloid β peptide [J].

Chen, KQ ;

Iribarren, P ;

Hu, JY ;

Chen, JH ;

Gong, WH ;

Cho, EH ;

Lockett, S ;

Dunlop, NM ;

Wang, JM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (06) :3651-3659

[7] Modulation of the purinergic P2X7 receptor attenuates lipopolysaccharide-mediated microglial activation and neuronal damage in inflamed brain [J].

Choi, Hyun B. ;

Ryu, Jae K. ;

Kim, Seung U. ;

McLarnon, James G. .

JOURNAL OF NEUROSCIENCE, 2007, 27 (18) :4957-4968

[8] Cysteinyl-leukotrienes are released from astrocytes and increase astrocyte proliferation and glial fibrillary acidic protein via cys-LT1 receptors and mitogen-activated protein kinase pathway [J].

Ciccarelli, R ;

D'Alimonte, I ;

Santavenere, C ;

D'Auro, M ;

Ballerini, P ;

Nargi, E ;

Buccella, S ;

Nicosia, S ;

Caciagli, F ;

Di Iorio, P .

EUROPEAN JOURNAL OF NEUROSCIENCE, 2004, 20 (06) :1514-1524

[9]

Combs CK, 1999, J NEUROSCI, V19, P928

[10] ATP mediates rapid microglial response to local brain injury in vivo [J].

Davalos, D ;

Grutzendler, J ;

Yang, G ;

Kim, JV ;

Zuo, Y ;

Jung, S ;

Littman, DR ;

Dustin, ML ;

Gan, WB .

NATURE NEUROSCIENCE, 2005, 8 (06) :752-758

← 1 2 3 4 5 6 →