Involvement of Adenosine A2A Receptors in Engulfment-Dependent Apoptotic Cell Suppression of Inflammation
摘要：
Efficient execution of apoptotic cell death followed by efficient clearance mediated by professional macrophages is a key mechanism in maintaining tissue homeostasis. Removal of apoptotic cells usually involves three central elements: 1) attraction of phagocytes via soluble "find me" signals, 2) recognition and phagocytosis via cell surface-presenting "eat me" signals, and 3) suppression or initiation of inflammatory responses depending on additional innate immune stimuli. Suppression of inflammation involves both direct inhibition of proinflammatory cytokine production and release of anti-inflammatory factors, which all contribute to the resolution of inflammation. In the current study, using wild-type and adenosine A(2A) receptor (A2AR) null mice, we investigated whether A2ARs, known to mediate anti-inflammatory signals in macrophages, participate in the apoptotic cell-mediated immunosuppression. We found that macrophages engulfing apoptotic cells release adenosine in sufficient amount to trigger A2ARs, and simultaneously increase the expression of A2ARs, as a result of possible activation of liver X receptor and peroxisome proliferators activated receptor δ. In macrophages engulfing apoptotic cells, stimulation of A2ARs suppresses the NO-dependent formation of neutrophil migration factors, such as macrophage inflammatory protein-2, using the adenylate cyclase/protein kinase A pathway. As a result, loss of A2ARs results in elevated chemoattractant secretion. This was evident as pronounced neutrophil migration upon exposure of macrophages to apoptotic cells in an in vivo peritonitis model. Altogether, our data indicate that adenosine is one of the soluble mediators released by macrophages that mediate engulfment-dependent apoptotic cell suppression of inflammation.
展开
关键词：
Bacillus Adenine Deoxyribonucleases, Type II Site-Specific Site-Specific DNA-Methyltransferase (Adenine-Specific Oligodeoxyribonucleotides DNA, Bacterial Electrophoresis, Agar Gel Electrophoresis, Polyacrylamide Gel Restriction Mapping Cloning, Molecular
DOI：
10.4049/jimmunol.1002284
被引量：
年份：
2011
国家科技图书文献中心
(权威机构)
Semantic Scholar
万方医学
万方医学
Semantic Scholar
(全网免费下载)
查看更多
掌桥科研
dx.doi.org
NCBI
Europe PMC
NCBI
(全网免费下载)
Europe PMC
(全网免费下载)
NCBI
JBC
ResearchGate
(全网免费下载)
ResearchGate
EBSCO
EBSCO
digital.csic.es
jimmunol.org
(全网免费下载)
hdl.handle.net
mysciencework.com
difusion.academiewb.be
embomm.embopress.org
mendeley.com
pubfacts.com
atvb.ahajournals.org
d.scholar.cnki.net
elifesciences.org
digital.csic.es
(全网免费下载)
jimmunol.org
www.socolar.com
onAcademic
difusion.ulb.ac.be
Semantic Scholar
(全网免费下载)
NCBI
(全网免费下载)
Europe PMC
(全网免费下载)
ResearchGate
(全网免费下载)
digital.csic.es
(全网免费下载)
jimmunol.org
(全网免费下载)
通过文献互助平台发起求助，成功后即可免费获取论文全文。
相似文献
参考文献
引证文献
辅助模式
引用
文献可以批量引用啦~
欢迎点我试用！
