PMID- 25245808
OWN - NLM
STAT- MEDLINE
DCOM- 20150112
LR  - 20211021
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 82
IP  - 12
DP  - 2014 Dec
TI  - Toll-like receptor-triggered calcium mobilization protects mice against bacterial 
      infection through extracellular ATP release.
PG  - 5076-85
LID - 10.1128/IAI.02546-14 [doi]
AB  - Extracellular ATP (eATP), released as a "danger signal" by injured or stressed 
      cells, plays an important role in the regulation of immune responses, but the 
      relationship between ATP release and innate immune responses is still uncertain. 
      In this study, we demonstrated that ATP was released through Toll-like receptor 
      (TLR)-associated signaling in both Escherichia coli-infected mice and 
      lipopolysaccharide (LPS)- or Pam3CSK4-treated macrophages. This ATP release could 
      be blocked completely only by N-ethylmaleimide (NEM), not by carbenoxolone (CBX), 
      flufenamic acid (FFA), or probenecid, suggesting the key role of exocytosis in 
      this process. Furthermore, LPS-induced ATP release could also be reduced 
      dramatically through suppressing calcium mobilization by use of U73122, caffeine, 
      and thapsigargin (TG). In addition, the secretion of interleukin-1beta (IL-1beta) and 
      CCL-2 was enhanced significantly by ATP, in a time- and dose-dependent manner. 
      Meanwhile, macrophage-mediated phagocytosis of bacteria was also promoted 
      significantly by ATP stimulation. Furthermore, extracellular ATP reduced the 
      number of invading bacteria and protected mice from peritonitis by activating 
      purinergic receptors. Mechanistically, phosphorylation of AKT and ERK was overtly 
      increased by ATP in antibacterial immune responses. Accordingly, if we blocked 
      the P2X- and P2Y-associated signaling pathway by using suramin and pyridoxal 
      phosphate-6-azo(benzene-2,4-disulfonic acid), tetrasodium salt (PPADS), the 
      ATP-enhanced immune response was restrained significantly. Taken together, our 
      findings reveal an internal relationship between danger signals and TLR signaling 
      in innate immune responses, which suggests a potential therapeutic significance 
      of calcium mobilization-mediated ATP release in infectious diseases.
CI  - Copyright (c) 2014, American Society for Microbiology. All Rights Reserved.
FAU - Ren, Hua
AU  - Ren H
AD  - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences 
      and School of Life Sciences, East China Normal University, Shanghai, China.
FAU - Teng, Yunfei
AU  - Teng Y
AD  - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences 
      and School of Life Sciences, East China Normal University, Shanghai, China.
FAU - Tan, Binghe
AU  - Tan B
AD  - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences 
      and School of Life Sciences, East China Normal University, Shanghai, China.
FAU - Zhang, Xiaoyu
AU  - Zhang X
AD  - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences 
      and School of Life Sciences, East China Normal University, Shanghai, China.
FAU - Jiang, Wei
AU  - Jiang W
AD  - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences 
      and School of Life Sciences, East China Normal University, Shanghai, China.
FAU - Liu, Mingyao
AU  - Liu M
AD  - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences 
      and School of Life Sciences, East China Normal University, Shanghai, China.
FAU - Jiang, Wenzheng
AU  - Jiang W
AD  - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences 
      and School of Life Sciences, East China Normal University, Shanghai, China.
FAU - Du, Bing
AU  - Du B
AD  - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences 
      and School of Life Sciences, East China Normal University, Shanghai, China 
      bdu.ecnu@gmail.com mqian@bio.ecnu.edu.cn.
FAU - Qian, Min
AU  - Qian M
AD  - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences 
      and School of Life Sciences, East China Normal University, Shanghai, China 
      bdu.ecnu@gmail.com mqian@bio.ecnu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140922
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Toll-Like Receptors)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenosine Triphosphate/*metabolism
MH  - Animals
MH  - Calcium/*metabolism
MH  - Disease Models, Animal
MH  - Escherichia coli/immunology
MH  - Escherichia coli Infections/*immunology/*prevention & control
MH  - Female
MH  - *Immunity, Innate
MH  - Lipopolysaccharides/immunology
MH  - Macrophages/drug effects/immunology
MH  - Mice, Inbred C57BL
MH  - Peritonitis/immunology/prevention & control
MH  - *Signal Transduction
MH  - Toll-Like Receptors/*immunology
PMC - PMC4249268
EDAT- 2014/09/24 06:00
MHDA- 2015/01/13 06:00
PMCR- 2015/06/01
CRDT- 2014/09/24 06:00
PHST- 2014/09/24 06:00 [entrez]
PHST- 2014/09/24 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
PHST- 2015/06/01 00:00 [pmc-release]
AID - IAI.02546-14 [pii]
AID - 02546-14 [pii]
AID - 10.1128/IAI.02546-14 [doi]
PST - ppublish
SO  - Infect Immun. 2014 Dec;82(12):5076-85. doi: 10.1128/IAI.02546-14. Epub 2014 Sep 
      22.