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

Cash, J.L., Bena, S., Headland, S.E., McArthur, S., Brancaleone, V. and Perretti, M. 2013. Chemerin15 inhibits neutrophil-mediated vascular inflammation and myocardial ischemia-reperfusion injury through ChemR23. EMBO reports. 14 (11), pp. 999-1007. https://doi.org/10.1038/embor.2013.138

TitleChemerin15 inhibits neutrophil-mediated vascular inflammation and myocardial ischemia-reperfusion injury through ChemR23
AuthorsCash, J.L., Bena, S., Headland, S.E., McArthur, S., Brancaleone, V. and Perretti, M.
Abstract

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.

JournalEMBO reports
Journal citation14 (11), pp. 999-1007
ISSN1469-3178
Year2013
PublisherWiley
Publisher's version
Digital Object Identifier (DOI)https://doi.org/10.1038/embor.2013.138
Publication dates
Published03 Sep 2013
LicenseCC BY 3.0

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Hannon, R., Croxtall, J.D., Getting, S.J., Roviezzo, F., Yona, S., Paul-Clark, M., Gavins, F.N.E., Perretti, M., Morris, J.F., Buckingham, J.C. and Flower, R.J. 2003. Aberrant inflammation and resistance to glucocorticoids in annexin 1-/- mouse. FASEB Journal. 17 (2), pp. 253-255. https://doi.org/10.1096/fj.02-0239fje

Dose- and sex-dependent effects of the neurotoxin 6-hydroxydopamine on the nigrostriatal dopaminergic pathway of adult rats: differential actions of estrogen in males and females
Murray, H.E., Pillai, A.V., McArthur, S., Razvi, N., Datla, K.P., Dexter, D.T. and Gillies, G.E. 2003. Dose- and sex-dependent effects of the neurotoxin 6-hydroxydopamine on the nigrostriatal dopaminergic pathway of adult rats: differential actions of estrogen in males and females. Neuroscience. 116 (1), pp. 213-222. https://doi.org/10.1016/S0306-4522(02)00578-X

Migration of specific leukocyte subsets in response to cytokine or chemokine application in vivo
Perretti, M. and Getting, S.J. 2003. Migration of specific leukocyte subsets in response to cytokine or chemokine application in vivo. Methods in Molecular Biology. 225, pp. 139-146. https://doi.org/10.1385/1-59259-374-7:139

Migration of specific leukocyte sub-sets in response to cytokine or chemokine application in vivo
Perretti, M. and Getting, S.J. 2003. Migration of specific leukocyte sub-sets in response to cytokine or chemokine application in vivo. in: Winyard, P.G. and Willoughby, D.A. (ed.) Inflammation Protocols Totowa, NJ Humana Press. pp. 139-146

The link module from human TSG-6 inhibits neutrophil migration in a hyaluronan- and inter-alpha -inhibitor-independent manner
Getting, S.J., Mahoney, D.J., Cao, T.V., Rugg, M.S., Fries, E., Milner, C.M., Perretti, M. and Day, A.J. 2002. The link module from human TSG-6 inhibits neutrophil migration in a hyaluronan- and inter-alpha -inhibitor-independent manner. Journal of Biological Chemistry. 277 (52), pp. 51068-51076. https://doi.org/10.1074/jbc.M205121200

The annexin-1 knockout mouse: what it tells us about the inflammatory response
Roviezzo, F., Getting, S.J., Paul-Clark, M., Yona, S., Gavins, F.N.E., Perretti, M., Hannon, R., Croxtall, J.D., Buckingham, J.C. and Flower, R.J. 2002. The annexin-1 knockout mouse: what it tells us about the inflammatory response. Journal of Physiology and Pharmacology. 53 (4, part 1), pp. 541 -553.

Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor
Perretti, M., Chiang, N., La, M., Fierro, I.M., Marullo, S., Getting, S.J., Solito, E. and Serhan, C.N. 2002. Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor. Nature Medicine. 8 (11), pp. 1296-1302. https://doi.org/10.1038/nm786

Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis
Getting, S.J., Christian, H.C., Flower, R.J. and Perretti, M. 2002. Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis. Arthritis & Rheumatism. 46 (10), pp. 2765-2775. https://doi.org/10.1002/art.10526

A novel control mechanism based on GDNF modulation of somatostatin release from sensory neurones
Malcangio, M., Getting, S.J., Grist, J., Cunningham, J.R., Bradbury, E.J., Issa, P.C., Lever, I.J., Pezet, S. and Perretti, M. 2002. A novel control mechanism based on GDNF modulation of somatostatin release from sensory neurones. FASEB Journal. 16 (7), pp. 730-732. https://doi.org/10.1096/fj.01-0971fje.

Characterization of CXC and CC chemokine expression in a murine model of chronic granuloma
Carollo, M., Getting, S.J., Delaney, S., Christie, M.I. and Perretti, M. 2002. Characterization of CXC and CC chemokine expression in a murine model of chronic granuloma. Inflammation Research. 51 (2), pp. 110-111. https://doi.org/10.1007/BF02684013

Involvement of the receptor for formylated peptides in the in vivo anti-migratory actions of annexin 1 and its mimetics
Perretti, M., Getting, S.J., Solito, E., Murphy, P.M. and Gao, J.L. 2001. Involvement of the receptor for formylated peptides in the in vivo anti-migratory actions of annexin 1 and its mimetics. American Journal of Pathology. 158 (6), pp. 1969-1973.

Anti-inflammatory effects of a novel, potent inhibitor of poly (ADP-ribose) polymerase
Mabley, J.G., Jagtap, P., Perretti, M., Getting, S.J., Salzman, A.L., Virag, L., Szabo, E., Soriano, F.G., Liaudet, L., Hasko, G., Marton, A., Southan, G.J., Abdelkarim, G.E. and Szabo, C. 2001. Anti-inflammatory effects of a novel, potent inhibitor of poly (ADP-ribose) polymerase. Inflammation Research. 50 (11), pp. 561-569. https://doi.org/10.1007/PL00000234

Arthritic diseases: melanocortin type 3 receptor agonists as potential therapeutics
Getting, S.J. and Perretti, M. 2001. Arthritic diseases: melanocortin type 3 receptor agonists as potential therapeutics. Current Opinion in Investigational Drugs. 2 (8), pp. 1064-1069.

Natural and synthetic agonists of the melanocortin receptor type 3 possess anti-inflammatory properties
Getting, S.J., Allcock, G.H., Flower, R.J. and Perretti, M. 2001. Natural and synthetic agonists of the melanocortin receptor type 3 possess anti-inflammatory properties. Journal of Leukocyte Biology. 69 (1), pp. 98-104.

MC3-R as a novel target for anti-inflammatory therapy
Getting, S.J. and Perretti, M. 2000. MC3-R as a novel target for anti-inflammatory therapy. Drug News & Perspectives. 13 (1), pp. 19-27.

POMC gene-derived peptides activate melanocortin type 3 receptor on murine macrophages, suppress cytokine release, and inhibit neutrophil migration in acute experimental inflammation
Getting, S.J., Gibbs, L., Clark, A.J.L., Flower, R.J. and Perretti, M. 1999. POMC gene-derived peptides activate melanocortin type 3 receptor on murine macrophages, suppress cytokine release, and inhibit neutrophil migration in acute experimental inflammation. Journal of Immunology. 162 (12), pp. 7446-7453.

Compounds for use in the treatment of inflammation
Flower, R.J., Getting, S.J. and Perretti, M. 1998. Compounds for use in the treatment of inflammation.

Inhibition of poly (ADP-ribose) synthetase attenuates neutrophil recruitment and exerts anti-inflammatory effects
Szabo, C., Lim, L.H.K., Cuzzocrea, S., Getting, S.J., Zingarelli, B., Flower, R.J., Salzman, A.L. and Perretti, M. 1997. Inhibition of poly (ADP-ribose) synthetase attenuates neutrophil recruitment and exerts anti-inflammatory effects. Journal of experimental medicine. 186 (7), pp. 1041-1049. https://doi.org/10.1084/jem.186.7.1041

Molecular determinants of monosodium urate crystal-induced murine peritonitis: a role for endogenous mast cells and a distinct requirement for endothelial-derived selectins
Getting, S.J., Flower, R.J., Parente, L., de Medicis, R., Lussier, A., Woliztky, B.A., Martins, M.A. and Perretti, M. 1997. Molecular determinants of monosodium urate crystal-induced murine peritonitis: a role for endogenous mast cells and a distinct requirement for endothelial-derived selectins. Journal of Pharmacology and Experimental Therapeutics. 283 (1), pp. 123-130.

Inhibition of neutrophil and monocyte recruitment by endogenous and exogenous lipocortin 1
Getting, S.J., Flower, R.J. and Perretti, M. 1997. Inhibition of neutrophil and monocyte recruitment by endogenous and exogenous lipocortin 1. British Journal of Pharmacology. 120 (6), pp. 1075-1082. https://doi.org/10.1038/sj.bjp.0701029

Sub-acute treatment of rats with dexamethasone reduces ICAM-1 levels on circulating monocytes
Tailor, A., Das, A.M., Getting, S.J., Flower, R.J. and Perretti, M. 1997. Sub-acute treatment of rats with dexamethasone reduces ICAM-1 levels on circulating monocytes. Biochemical and Biophysical Research Communications. 231 (3), pp. 675-678. https://doi.org/10.1006/bbrc.1997.6168

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