Neutrophil transfer of miR-223 to lung epithelial cells dampens acute lung injury in mice

被引：170

作者：

Neudecker, Viola ^{[1
,2
]}

Brodsky, Kelley S. ^{[1
]}

Clambey, Eric T. ^{[1
]}

Schmidt, Eric P. ^{[1
,3
]}

Packard, Thomas A. ^{[4
,5
]}

Davenport, Bennett ^{[1
]}

Standiford, Theodore J. ^{[6
]}

Weng, Tingting ^{[7
]}

Fletcher, Ashley A. ^{[8
]}

Barthel, Lea ^{[9
]}

Masterson, Joanne C. ^{[10
,11
]}

Furuta, Glenn T. ^{[10
,11
]}

Cai, Chunyan ^{[12
]}

Blackburn, Michael R. ^{[7
]}

Ginde, Adit A. ^{[1
,13
]}

Graner, Michael W. ^{[14
]}

Janssen, William J. ^{[1
,9
]}

Zemans, Rachel L. ^{[9
]}

Evans, Christopher M. ^{[1
,8
]}

Burnham, Ellen L. ^{[8
]}

Homann, Dirk ^{[1
]}

Moss, Marc ^{[8
]}

Kreth, Simone ^{[2
]}

Zacharowski, Kai ^{[15
]}

Henson, Peter M. ^{[1
,4
,5
]}

Eltzschig, Holger K. ^{[1
,16
]}

机构：

[1] Univ Colorado Denver, Dept Anesthesiol, Organ Protect Program, Aurora, CO 80045 USA

[2] Ludwig Maximilian Univ Munich, Univ Hosp, Dept Anesthesiol, D-81377 Munich, Germany

[3] Univ Colorado, Sch Med, Dept Med, 3Program Translat Lung Res, Aurora, CO 80045 USA

[4] Univ Colorado, Sch Med, Dept Immunol & Microbiol, Denver, CO 80206 USA

[5] Natl Jewish Hlth, Denver, CO 80206 USA

[6] Univ Michigan, Med Sch, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA

[7] Univ Texas Houston, Med Sch, Dept Biochem & Mol Biol, Houston, TX 77030 USA

[8] Univ Colorado, Sch Med, Dept Med, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA

[9] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA

[10] Univ Colorado, Sect Pediat Gastroenterol Hepatol & Nutr, Gastrointestinal Eosinophil Dis Program, Dept Pediat,Digest Hlth Inst,Childrens Hosp Color, Aurora, CO 80045 USA

[11] Univ Colorado, Dept Med, Mucosal Inflammat Program, Sch Med, Aurora, CO 80045 USA

[12] Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, McGovern Med Sch, Houston, TX 77030 USA

[13] Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO 80045 USA

[14] Univ Colorado Denver, Dept Neurosurg, Aurora, CO 80045 USA

[15] Univ Hosp Frankfurt, Dept Anesthesiol Intens Care Med & Pain Therapy, D-60590 Frankfurt, Germany

[16] Univ Texas Hlth Sci Ctr Houston, Dept Anesthesiol, McGovern Med Sch, Houston, TX 77030 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2017年 / 9卷 / 408期

基金：

新加坡国家研究基金会;

关键词：

ALVEOLAR TYPE-II; POLY(ADP-RIBOSE) POLYMERASE-1; INTERCELLULAR COMMUNICATION; MEDIATED ENDOCYTOSIS; ADENOSINE; MICRORNA-223; MECHANISM; MICROPARTICLES; VENTILATION; RESOLUTION;

D O I：

10.1126/scitranslmed.aah5360

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Intercellular transfer of microRNAs can mediate communication between critical effector cells. We hypothesized that transfer of neutrophil-derived microRNAs to pulmonary epithelial cells could alter mucosal gene expression during acute lung injury. Pulmonary-epithelial microRNA profiling during coculture of alveolar epithelial cells with polymorphonuclear neutrophils (PMNs) revealed a selective increase in lung epithelial cell expression of microRNA-223 (miR223). Analysis of PMN-derived supernatants showed activation-dependent release of miR-223 and subsequent transfer to alveolar epithelial cells during coculture in vitro or after ventilator-induced acute lung injury in mice. Genetic studies indicated that miR-223 deficiency was associatedwith severe lung inflammation, whereas pulmonary overexpression of miR-223 in mice resulted in protection during acute lung injury induced by mechanical ventilation or by infection with Staphylococcus aureus. Studies of putative miR-223 gene targets implicated repression of poly(adenosine diphosphateribose) polymerase-1 (PARP-1) in the miR-223-dependent attenuation of lung inflammation. Together, these findings suggest that intercellular transfer of miR-223 from neutrophils to pulmonary epithelial cells may dampen acute lung injury through repression of PARP-1

引用

页数：19

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