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{"title"=>"Adenosine-5'-Triphosphate (ATP) Protects Mice against Bacterial Infection by Activation of the NLRP3 Inflammasome", "type"=>"journal", "authors"=>[{"first_name"=>"Yang", "last_name"=>"Xiang", "scopus_author_id"=>"57079475300"}, {"first_name"=>"Xuan", "last_name"=>"Wang", "scopus_author_id"=>"55745271500"}, {"first_name"=>"Chao", "last_name"=>"Yan", "scopus_author_id"=>"57199762690"}, {"first_name"=>"Qian", "last_name"=>"Gao", "scopus_author_id"=>"56391644100"}, {"first_name"=>"Sheng An", "last_name"=>"Li", "scopus_author_id"=>"55221306600"}, {"first_name"=>"Jie", "last_name"=>"Liu", "scopus_author_id"=>"55261296500"}, {"first_name"=>"Kaifeng", "last_name"=>"Zhou", "scopus_author_id"=>"55744514600"}, {"first_name"=>"Xiaolong", "last_name"=>"Guo", "scopus_author_id"=>"55744955600"}, {"first_name"=>"Wenhui", "last_name"=>"Lee", "scopus_author_id"=>"7407091493"}, {"first_name"=>"Yun", "last_name"=>"Zhang", "scopus_author_id"=>"55885635000"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84878077028", "doi"=>"10.1371/journal.pone.0063759", "pui"=>"368973438", "pmid"=>"23717478", "scopus"=>"2-s2.0-84878077028", "issn"=>"19326203", "isbn"=>"1932-6203"}, "id"=>"a5f34a12-a774-35a9-b726-817814725ee4", "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.", "link"=>"http://www.mendeley.com/research/adenosine5triphosphate-atp-protects-mice-against-bacterial-infection-activation-nlrp3-inflammasome", "reader_count"=>35, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>4, "Researcher"=>10, "Student > Ph. D. Student"=>13, "Student > Master"=>2, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>4, "Researcher"=>10, "Student > Ph. D. Student"=>13, "Student > Master"=>2, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>18, "Medicine and Dentistry"=>5, "Immunology and Microbiology"=>9}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>9}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "Japan"=>2, "Brazil"=>1, "Spain"=>1}, "group_count"=>0}

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• http://doi.org/10.1007/s12032-014-0387-8
• http://doi.org/10.1002/ange.201401035
• http://doi.org/10.1038/srep44625
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• http://doi.org/10.3390/biom5020775

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/1548646"], "description"=>"<p>(<b>A</b>) <i>In vitro</i> analysis of ATP released from BMDMs and bacteria. The ATP levels in the culture medium from wells containing only cells, only bacteria (3×10⁸ CFU/ml) or both were assessed after 0.5, 1 and 2 hour of incubation. The data are presented as the means±SEMs (n = 5). (<b>B</b>) <i>In vivo</i> analysis of ATP release from murine peritoneal cells. Mice received intraperitoneal injections of E.coli 25922 (3×10⁸ CFU per mouse) or S. aureus 25923 (3×10⁸ CFU per mouse). The mice were sacrificed 0.5, 1 or 2 hours after injection. The peritoneal lavage fluid was harvested by injecting 2 ml of PBS into the peritoneum. The ATP concentration in the fluid was then assayed. As a negative control, 150 µl of 0.9% NaCl was intraperitoneally injected, and the peritoneal lavage fluid was harvested 2 hours after NaCl injection. The data are presented as the means±SEMs (n = 10). Values that are significantly different different are indicated by asterisks as follows: **, P<0.01.</p>", "links"=>[], "tags"=>["immunology", "immunity", "inflammation", "Innate immunity", "Immune response", "microbiology", "Clinical immunology", "released"], "article_id"=>1069004, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Yang Xiang", "Xuan Wang", "Chao Yan", "Qian Gao", "Sheng-An Li", "Jie Liu", "Kaifeng Zhou", "Xiaolong Guo", "Wenhui Lee", "Yun Zhang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0063759.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ATP_was_released_after_infection_both_in_vitro_and_in_vivo_/1069004", "title"=>"ATP was released after infection both <i>in vitro</i> and <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-22 07:54:12"}
• {"files"=>["https://ndownloader.figshare.com/files/1548655"], "description"=>"<p>(<b>A, B and C</b>) BMDMs were primed with LPS (500 ng/ml), heat killed <i>E. coli</i> 25922 (HKEC) (3×10⁸ CFU/ml) or heat killed <i>S. aureus</i> 25923 (HKSA) (3×10⁸ CFU/ml) and the medium was replaced with fresh serum-free medium and incubated with ATP (2 mM) for 0.5, 1, 2, 6, 12 and 24 hours. The levels of IL-1β, KC and MIP-2 were then assessed by ELISA. (<b>D, E and F</b>) To test the role of caspase-1 in the cytokine secretion, the cells were pre-incubated with the Caspase-1 inhibitor Ac-YVAD-cho (50 µM) for 30 min after LPS-priming, then incubated with ATP. The data are presented as the means±SEMs (n = 5). Values that are significantly different are indicated by asterisks; *(P<0.05), **(P<0.01). Values that showed no significant differences are marked “ns”. (<b>G</b>) BMDMs incubated with ATP (2 mM) for the indicated times were lysed and immunoblotted with Caspase-1 antibody (Santa Cruz). The appearance of the p10 subunit represented the activation of caspase-1 and the inflammasome. The presented graph is representative of at least three independent experiments. (<b>H</b>) ATP-stimulated culture medium was harvested, and the ability to induce neutrophil chemotaxis was assessed using 3-µm-pore transwells. The data are presented as the means±SEMs (n = 5). The number of migrated cells was compared with the control (containing fresh medium in the lower chamber), and the values that are significantly different are indicated by asterisks as follows: *(P<0.05), **(P<0.01).</p>", "links"=>[], "tags"=>["immunology", "immunity", "inflammation", "Innate immunity", "Immune response", "microbiology", "Clinical immunology", "stimulats", "cytokine", "chemokine", "secretion", "inflammasome", "activation", "indirectly", "neutrophil"], "article_id"=>1069013, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Yang Xiang", "Xuan Wang", "Chao Yan", "Qian Gao", "Sheng-An Li", "Jie Liu", "Kaifeng Zhou", "Xiaolong Guo", "Wenhui Lee", "Yun Zhang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0063759.g002", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ATP_stimulats_cytokine_and_chemokine_secretion_and_inflammasome_activation_directly_and_indirectly_induces_in_vitro_neutrophil_chemotaxis_/1069013", "title"=>"ATP stimulats cytokine and chemokine secretion and inflammasome activation directly and indirectly induces <b><i>in vitro</i></b><b> neutrophil chemotaxis.</b>", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-22 07:54:12"}
• {"files"=>["https://ndownloader.figshare.com/files/1548676"], "description"=>"<p>(<b>A</b>) YVAD (5 mg/kg), Apyrase (50 U/kg) or BBG (60 mg/kg) pre-injection prior to ATP reduced the survival rate of the mice infected with <i>E. coli</i> 25922 (n = 10, P<0.05 by log-rank test). (<b>B</b>) YVAD (5 mg/kg), Apyrase (50 U/kg) or BBG (60 mg/kg) pre-injection before ATP reduced the survival rate of mice infected with <i>S. aureu</i>s 25923 (n = 10, P<0.05 by log-rank test).</p>", "links"=>[], "tags"=>["immunology", "immunity", "inflammation", "Innate immunity", "Immune response", "microbiology", "Clinical immunology", "p2x7", "inhibition", "caspase-1", "inflammasome", "attenuated", "atp", "bacterial"], "article_id"=>1069026, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Yang Xiang", "Xuan Wang", "Chao Yan", "Qian Gao", "Sheng-An Li", "Jie Liu", "Kaifeng Zhou", "Xiaolong Guo", "Wenhui Lee", "Yun Zhang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0063759.g005", "stats"=>{"downloads"=>1, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ATP_degradation_P2X7_inhibition_and_Caspase_1_and_inflammasome_inhibition_attenuated_the_protective_effect_of_ATP_against_bacterial_infection_/1069026", "title"=>"ATP degradation, P2X7 inhibition and Caspase-1 and inflammasome inhibition attenuated the protective effect of ATP against bacterial infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-22 07:54:12"}
• {"files"=>["https://ndownloader.figshare.com/files/1548667"], "description"=>"<p>(<b>A</b>) The pre-injection of ATP (50 mg/kg) 1, 4, or 24 hours before bacterial challenge <i>(E. coli</i>, ATCC25922, 2×10⁸/mice) manifested different potentials to protect mice against bacterial infection (n = 10, P<0.05 by log-rank test). (<b>B</b>) The pre-injection of ATP (50 mg/kg) 4 hours before bacterial challenge (<i>S. aureus</i>, ATCC25923, 5×10⁸/mouse) manifested a different ability to protect mice from bacterial infection (n = 10, P<0.05 by log-rank test). (<b>C</b>) Bacterial counts in the mouse peritoneum 12 hours after the bacterial (E. coli, ATCC25922, 2×10⁸/mice) challenge (n = 10, P<0.05 by t test). Dead animals were assigned the highest CFU count obtained in the experiment. ATP pre-administration (4 hours before bacterial challenge) markedly reduced the bacteria counts in the mouse peritoneum. (<b>D</b>) Bacterial counts in the mouse peritoneum 12 hours after the bacterial (<i>S. aureus</i>, ATCC25923, 5×10⁸/mouse) challenge (n = 10, P<0.05 by t test). Dead animals were assigned the highest CFU count obtained in the experiment. ATP pre-administration (4 hours before bacterial challenge) markedly reduced the bacterial counts in the mouse peritoneum. (E) Pre-injection of ATP (50 mg/kg) 4 hours before the bacteria challenge (E. coli, clinically isolated, 2×10⁸/mouse) reduced the mortality rate from 90% to 40% (n = 10, P<0.05 by log-rank test). (F) Pre-injection of ATP (50 mg/kg) 4 hours before the bacteria challenge (<i>S. aureus</i>, clinically isolated, 5×10⁸/mice) reduced the mortality rate from 100% to 20% (n = 10, P<0.05 by log-rank test).</p>", "links"=>[], "tags"=>["immunology", "immunity", "inflammation", "Innate immunity", "Immune response", "microbiology", "Clinical immunology", "protected", "mice", "bacterial"], "article_id"=>1069017, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Yang Xiang", "Xuan Wang", "Chao Yan", "Qian Gao", "Sheng-An Li", "Jie Liu", "Kaifeng Zhou", "Xiaolong Guo", "Wenhui Lee", "Yun Zhang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0063759.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ATP_protected_mice_from_bacterial_infection_/1069017", "title"=>"ATP protected mice from bacterial infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-22 07:54:12"}
• {"files"=>["https://ndownloader.figshare.com/files/1548678"], "description"=>"<p>During bacterial infection, ATP was released by both the infected cells and the bacteria. The released ATP is able to facilitate neutrophil recruitment to the site of infection by three potential mechanisms: (1) directly enhancing neutrophil chemotaxis; (2) inducing chemokine secretion from resident macrophages through the activation of P2Y receptors; (3) inducing NLRP3 inflammasome activation and Interleukin-1β secretion through the P2X7 receptor, while Interleukin-1β further enhances chemokine secretion. The early recruitment of neutrophils facilitated the clearance of bacteria and the survival rate in mice.</p>", "links"=>[], "tags"=>["immunology", "immunity", "inflammation", "Innate immunity", "Immune response", "microbiology", "Clinical immunology", "atp", "facilitating", "bacterial"], "article_id"=>1069028, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Yang Xiang", "Xuan Wang", "Chao Yan", "Qian Gao", "Sheng-An Li", "Jie Liu", "Kaifeng Zhou", "Xiaolong Guo", "Wenhui Lee", "Yun Zhang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0063759.g006", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_model_for_the_role_of_ATP_in_facilitating_the_host_defense_against_bacterial_infection_/1069028", "title"=>"A model for the role of ATP in facilitating the host defense against bacterial infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-22 07:54:12"}
• {"files"=>["https://ndownloader.figshare.com/files/1548673"], "description"=>"<p>(<b>A, B and C</b>) ATP (50 mg/kg) injection promoted the secretion of IL-1β, KC and MIP-2. Ac-YVAD-cho (5 mg/kg) attenuated the secretion of IL-1β, KC and MIP-2 induced by ATP. The data are presented as the means±SEMs (n = 6). The values that are significantly different are indicated by asterisks; **(P<0.01). The values with no significant differences were marked as “ns”. (<b>D</b>) Peritoneal exudate cells were stained and analyzed. Gr-1^lowF4/80^high cells represent peritoneal monocytes and Gr-1^high F4/80^low cells represent recruited neutrophils. The data are representative of three independent experiments.</p>", "links"=>[], "tags"=>["immunology", "immunity", "inflammation", "Innate immunity", "Immune response", "microbiology", "Clinical immunology", "atp-induced", "cytokine", "chemokine", "secretion", "neutrophil", "recruitment", "caspase-1", "inflammasome"], "article_id"=>1069023, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Yang Xiang", "Xuan Wang", "Chao Yan", "Qian Gao", "Sheng-An Li", "Jie Liu", "Kaifeng Zhou", "Xiaolong Guo", "Wenhui Lee", "Yun Zhang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0063759.g004", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_ATP_induced_cytokine_and_chemokine_secretion_and_neutrophil_recruitment_in_vivo_are_partially_dependent_on_caspase_1_and_inflammasome_activation_/1069023", "title"=>"The ATP-induced cytokine and chemokine secretion and neutrophil recruitment <i>in vivo</i> are partially dependent on caspase-1 and inflammasome activation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-22 07:54:12"}

PMC Usage Stats | Further Information

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Relative Metric

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F1000Prime