DAP12 expression in lung macrophages mediates ischemia/reperfusion injury by promoting neutrophil extravasation.
DAP12 expression in lung macrophages mediates ischemia/reperfusion injury by promoting neutrophil extravasation.
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DOI：
10.4049/jimmunol.1401415
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发表时间：
2015-04-15
期刊：
影响因子：
--
通讯作者：
Kreisel D
中科院分区：
文献类型：
--
作者：
Spahn JH;Li W;Bribriesco AC;Liu J;Shen H;Ibricevic A;Pan JH;Zinselmeyer BH;Brody SL;Goldstein DR;Krupnick AS;Gelman AE;Miller MJ;Kreisel D
Neutrophils are critical mediators of innate immune responses and contribute to tissue injury. However, immune pathways that regulate neutrophil recruitment to injured tissues during noninfectious inflammation remain poorly understood. DAP12 is a cell-membrane associated protein that is expressed in myeloid cells and can either augment or dampen innate inflammatory responses during infections. To elucidate the role of DAP12 in pulmonary ischemia-reperfusion injury, we took advantage of a clinically relevant mouse model of transplant-mediated lung ischemia reperfusion injury. This technique allowed us to dissect the importance of DAP12 in tissue-resident cells and those that infiltrate injured tissue from the periphery during noninfectious inflammation. Macrophages in both mouse and human lungs that have been subjected to cold ischemic storage express DAP12. We found that donor, but not recipient deficiency in DAP12 protected against pulmonary ischemia reperfusion injury. Analysis of the immune response showed that DAP12 promotes the survival of tissue-resident alveolar macrophages and contributes to local production of neutrophil chemoattractants. Intravital imaging demonstrated a transendothelial migration defect into DAP12-deficient lungs, which can be rescued by local administration of the neutrophil chemokine CXCL2. We have uncovered a previously unrecognized role for DAP12 expression in tissue-resident alveolar macrophages in mediating acute noninfectious tissue injury through regulation of neutrophil trafficking.
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