A Potential Role for P2X7R in Allergic Airway Inflammation in Mice and Humans

被引：123

作者：

Mueller, Tobias ^{[1
]}

Vieira, Rodolfo Paula ^{[1
]}

Grimm, Melanie ^{[1
]}

Duerk, Thorsten ^{[1
]}

Cicko, Sanja ^{[1
]}

Zeiser, Robert ^{[2
]}

Jakob, Thilo ^{[3
]}

Martin, Stefan F. ^{[3
]}

Blumenthal, Britta ^{[1
]}

Sorichter, Stephan ^{[1
]}

Ferrari, Davide ^{[4
]}

Di Virgillio, Francesco ^{[4
]}

Idzko, Marco ^{[1
]}

机构：

[1] Univ Med Ctr Freiburg, Dept Pneumol, D-79106 Freiburg, Germany

[2] Univ Med Ctr Freiburg, Dept Oncol, D-79106 Freiburg, Germany

[3] Univ Med Ctr Freiburg, Allergy Res Grp, D-79106 Freiburg, Germany

[4] Univ Ferrara, Dept Gen Pathol, I-44100 Ferrara, Italy

来源：

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY | 2011年 / 44卷 / 04期

关键词：

asthma; P2X(7); ATP; dendritic cells; eosinophils; EXTRACELLULAR ADENOSINE-TRIPHOSPHATE; OBSTRUCTIVE PULMONARY-DISEASE; DENDRITIC CELL-FUNCTION; P2X RECEPTORS; ATP TRIGGERS; URIC-ACID; ASTHMA; NUCLEOTIDES; ACTIVATION; RELEASE;

D O I：

10.1165/rcmb.2010-0129OC

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

P2X(7)R deficiency is associated with a less severe outcome in acute and chronic inflammatory disorders. Recently, we demonstrated that extracellular adenosine triphosphate is involved in the pathogenesis of asthma by modulating the function of dendritic cells (DCs). However, the role of the purinergic receptor subtype P2X(7) is unknown. To elucidate the role of P2X(7)R in allergic airway inflammation (AAI) in vitro and in vivo, P2X(7)R expression was measured in lung tissue and immune cells of mice or in humans with allergic asthma. By using a specific P2X(7)R-antagonist and P2X(7)R-deficient animals, the role of this receptor in acute and chronic experimental asthma was explored. P2X(7)R was found to be up-regulated during acute and chronic asthmatic airway inflammation in mice and humans. In vivo experiments revealed the functional relevance of this finding because selective P2X(7)R inhibition or P2X(7)R deficiency was associated with reduced features of acute and chronic asthma in the ovalbumin-alum or HDM model of AAI. Experiments with bone marrow chimeras emphasized that P2X(7)R expression on hematopoietic cells is responsible for the proasthmatic effects of P2X(7)R signaling. In the DC-driven model of AAI, P2X(7)R-deficient DCs showed a reduced capacity to induce Th2 immunity in vivo. Upregulation of P2X(7)R on BAL macrophages and blood eosinophils could be observed in patients with chronic asthma. Our data suggest that targeting P2X(7)R on hematopoietic cells (e.g., DCs or eosinophils) might be a new therapeutic option for the treatment of asthma.

引用

页码：456 / 464

页数：9

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