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PMID: 23717478 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Adenosine-5'-triphosphate (ATP) protects mice against bacterial infection by activation of the NLRP3 inflammasome.

PloS one ·Vol. 8 ·No. 5 ·2013-00-00 ·Pages e63759

Xiang Y, Wang X, Yan C, Gao Q, Li SA, Liu J, Zhou K, Guo X, Lee W, Zhang Y

Abstract

It has been established that Adenosine-5'-triphosphate (ATP) can activate the NLRP3 inflammasome. However, the physiological effect of extracellular ATP on NLRP3 inflammasome activation has not yet been investigated. In the present study, we found that ATP was indeed released during bacterial infection. By using a murine peritonitis model, we also found that ATP promotes the fight against bacterial infection in mice. ATP induced the secretion of IL-1β and chemokines by murine bone marrow-derived macrophages in vitro. Furthermore, the intraperitoneal injection of ATP elevated the levels of IL-1β and chemokines in the mouse peritoneal lavage. Neutrophils were rapidly recruited to the peritoneum after ATP injection. In addition, the effects on cytokine and chemokine secretion and neutrophil recruitment were markedly attenuated by the pre-administration of the caspase-1 inhibitor Ac-YVAD-cho. Ac-YVAD-cho also significantly attenuated the protective effect of ATP against bacterial infection. In the present study, we demonstrated a protective role for ATP during bacterial infection and this effect was related to NLRP3 inflammasome activation. Together, these results suggest a role for ATP in initiating the immune response in hosts suffering from infections.

MeSH Terms
Adenosine Triphosphate/immunology,metabolism Animals Bacterial Infections/immunology,metabolism,prevention & control Carrier Proteins/immunology,metabolism Caspase 1/immunology,metabolism Chemokine CXCL2/immunology,metabolism Inflammasomes/immunology,metabolism Interleukin-1beta/immunology,metabolism Macrophages/immunology,metabolism Male Mice NLR Family, Pyrin Domain-Containing 3 Protein Neutrophil Infiltration/immunology Neutrophils/immunology,metabolism Peritonitis/immunology,metabolism
Chemicals
Carrier Proteins Chemokine CXCL2 Cxcl2 protein, mouse Inflammasomes Interleukin-1beta NLR Family, Pyrin Domain-Containing 3 Protein Nlrp3 protein, mouse Adenosine Triphosphate Caspase 1
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Xiang Yang
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
Wang Xuan
Yan Chao
Gao Qian
Li Sheng-An
Liu Jie
Zhou Kaifeng
Guo Xiaolong
Lee Wenhui
Zhang Yun
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0063759
Published
2013-00-00
Epub
2013-00-22
Pages
e63759
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3661663
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0063759 PMC Full Text View journal details
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