Chemerin15 inhibits neutrophil-mediated vascular inflammation and myocardial ischemia-reperfusion injury through ChemR23

被引:43
作者
Cash, Jenna L. [1 ]
Bena, Stefania [1 ]
Headland, Sarah E. [1 ]
McArthur, Simon [1 ]
Brancaleone, Vincenzo [1 ]
Perretti, Mauro [1 ]
机构
[1] Barts & London Queen Marys Sch Med & Dent, William Harvey Res Inst, London, England
基金
英国惠康基金;
关键词
chemerin peptide; inflammation; intravital microscopy; neutrophil; resolution; NECROSIS-FACTOR-ALPHA; LEUKOCYTE ADHESION; L-SELECTIN; INTEGRIN ACTIVATION; SRC KINASES; IMMUNITY; RECEPTOR; CELLS; P38;
D O I
10.1038/embor.2013.138
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Neutrophil activation and adhesion must be tightly controlled to prevent complications associated with excessive inflammatory responses. The role of the anti-inflammatory peptide chemerin15 (C15) and the receptor ChemR23 in neutrophil physiology is unknown. Here, we report that ChemR23 is expressed in neutrophil granules and rapidly upregulated upon neutrophil activation. C15 inhibits integrin activation and clustering, reducing neutrophil adhesion and chemotaxis in vitro. In the inflamed microvasculature, C15 rapidly modulates neutrophil physiology inducing adherent cell detachment from the inflamed endothelium, while reducing neutrophil recruitment and heart damage in a murine myocardial infarction model. These effects are mediated through ChemR23. We identify the C15/ChemR23 pathway as a new regulator and thus therapeutic target in neutrophil-driven pathologies.
引用
收藏
页码:999 / 1007
页数:9
相关论文
共 30 条
[1]   Neutrophil granules: a library of innate immunity proteins [J].
Borregaard, Niels ;
Sorensen, Ole E. ;
Theilgaard-Wnchl, Kim .
TRENDS IN IMMUNOLOGY, 2007, 28 (08) :340-345
[2]   TNF-induced β2 integrin activation involves Src kinases and a redox-regulated activation of p38 MAPK [J].
Bouaouina, M ;
Blouin, E ;
Halbwachs-Mecarelli, L ;
Lesavre, P ;
Rieu, P .
JOURNAL OF IMMUNOLOGY, 2004, 173 (02) :1313-1320
[3]   Evidence for an Anti-Inflammatory Loop Centered on Polymorphonuclear Leukocyte Formyl Peptide Receptor 2/Lipoxin A4 Receptor and Operative in the Inflamed Microvasculature [J].
Brancaleone, Vincenzo ;
Dalli, Jesmond ;
Bena, Stefania ;
Flower, Roderick J. ;
Cirino, Giuseppe ;
Perretti, Mauro .
JOURNAL OF IMMUNOLOGY, 2011, 186 (08) :4905-4914
[4]   Synthetic chemerin-derived peptides suppress inflammation through ChemR23 [J].
Cash, Jenna L. ;
Hart, Rosie ;
Russ, Andreas ;
Dixon, John P. C. ;
Colledge, William H. ;
Doran, Joanne ;
Hendrick, Alan G. ;
Carlton, Mark B. L. ;
Greaves, David R. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (04) :767-775
[5]   Chemerin Peptides Promote Phagocytosis in a ChemR23-and Syk-Dependent Manner [J].
Cash, Jenna L. ;
Christian, Annabel R. ;
Greaves, David R. .
JOURNAL OF IMMUNOLOGY, 2010, 184 (09) :5315-5324
[6]   Lack of Neutrophil-Derived CRAMP Reduces Atherosclerosis in Mice [J].
Doering, Yvonne ;
Drechsler, Maik ;
Wantha, Sarawuth ;
Kemmerich, Klaus ;
Lievens, Dirk ;
Vijayan, Santosh ;
Gallo, Richard L. ;
Weber, Christian ;
Soehnlein, Oliver .
CIRCULATION RESEARCH, 2012, 110 (08) :1052-U73
[7]   Structure-function relationship and role of tumor necrosis factor-α-converting enzyme in the down-regulation of L-selectin by non-steroidal anti-inflammatory drugs [J].
Gómez-Gaviro, MV ;
González-Alvaro, I ;
Domínguez-Jiménez, C ;
Peschon, J ;
Black, RA ;
Sánchez-Madrid, F ;
Díaz-González, F .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (41) :38212-38221
[8]   L-selectin shedding regulates leukocyte recruitment [J].
Hafezi-Moghadam, A ;
Thomas, KL ;
Prorock, AJ ;
Huo, YQ ;
Ley, K .
JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 193 (07) :863-872
[9]   Integrin signalling at a glance [J].
Harburger, David S. ;
Calderwood, David A. .
JOURNAL OF CELL SCIENCE, 2009, 122 (02) :159-163
[10]   The role of neutrophils in myocardial ischemia-reperfusion injury [J].
Jordan, JE ;
Zhao, ZQ ;
Vinten-Johansen, J .
CARDIOVASCULAR RESEARCH, 1999, 43 (04) :860-878