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

Jean-Eric Alard, Almudena Ortega-Gomez, Kanin Wichapong, Dario Bongiovanni, Michael Horckmans, Remco T. A. Megens, Giovanna Leoni, Bartolo Ferraro, Jan Rossaint, Nicole Paulin, Judy Ng, Hans Ippel, Dennis Suylen, Rabea Hinkel, Xavier Blanchet, Fanny Gaillard, Michele D'Amico, Phillipp von Hundelshausen, Alexander Zarbock, Christoph ScheiermannTilman M. Hackeng, Sabine Steffens, Christian Kupatt, Gerry A. F. Nicolaes, Christian Weber, Oliver Soehnlein*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

83 Citations (Web of Science)


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, a-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.
Original languageEnglish
Article number317ra196
JournalScience Translational Medicine
Issue number317
Publication statusPublished - 9 Dec 2015

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