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Recruitment of classical monocytes can be inhibited by disturbing heteromers of neutrophil HNP1 and platelet CCL5

Alard, Jean-Eric
Ortega-Gomez, Almudena
Wichapong, Kanin
Bongiovanni, Dario
Horckmans, Michael
Megens, Remco T A
Leoni, Giovanna
Ferraro, Bartolo
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Published in Science Translational Medicine. 2015, vol. 7, no. 317, 317ra196
Abstract In acute and chronic inflammation, neutrophils and platelets, both of which promote monocyte recruitment, are often activated simultaneously. We investigated how secretory products of neutrophils and platelets synergize to enhance the recruitment of monocytes. We found that neutrophil-borne human neutrophil peptide 1 (HNP1, α-defensin) and platelet-derived CCL5 form heteromers. These heteromers stimulate monocyte adhesion through CCR5 ligation. We further determined structural features of HNP1-CCL5 heteromers and designed a stable peptide that could disturb proinflammatory HNP1-CCL5 interactions. This peptide attenuated monocyte and macrophage recruitment in a mouse model of myocardial infarction. These results establish the in vivo relevance of heteromers formed between proteins released from neutrophils and platelets and show the potential of targeting heteromer formation to resolve acute or chronic inflammation.
Keywords Blood Platelets/metabolismCell AdhesionChemokine CCL5/metabolismHuman Umbilical Vein Endothelial Cells/metabolismHumansMonocytes/cytology/metabolismMyocardium/cytologyNeutrophils/cytology/metabolismProtein BindingProtein Multimerizationalpha-Defensins/metabolism
PMID: 26659570
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Research group Groupe Christoph Scheiermann (995)
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ALARD, Jean-Eric et al. Recruitment of classical monocytes can be inhibited by disturbing heteromers of neutrophil HNP1 and platelet CCL5. In: Science Translational Medicine, 2015, vol. 7, n° 317, p. 317ra196. doi: 10.1126/scitranslmed.aad5330

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Deposited on : 2018-11-28

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