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

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.

journal_name

Sci Transl Med

journal_title

Science translational medicine

authors

Alard JE,Ortega-Gomez A,Wichapong K,Bongiovanni D,Horckmans M,Megens RT,Leoni G,Ferraro B,Rossaint J,Paulin N,Ng J,Ippel H,Suylen D,Hinkel R,Blanchet X,Gaillard F,D'Amico M,von Hundelshausen P,Zarbock A,Scheiermann

doi

10.1126/scitranslmed.aad5330

subject

Has Abstract

pub_date

2015-12-09 00:00:00

pages

317ra196

issue

317

eissn

1946-6234

issn

1946-6242

pii

7/317/317ra196

journal_volume

7

pub_type

杂志文章

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