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 Scheiermann; Tilman M. Hackeng; Sabine Steffens; Christian Kupatt; Gerry A. F. Nicolaes; Christian Weber; Oliver Soehnlein

doi:10.1126/scitranslmed.aad5330

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 journal › Article › Academic › peer-review

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, 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 language	English
Article number	317ra196
Journal	Science Translational Medicine
Volume	7
Issue number	317
DOIs	https://doi.org/10.1126/scitranslmed.aad5330
Publication status	Published - 9 Dec 2015

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Alard, J.-E., Ortega-Gomez, A., Wichapong, K., Bongiovanni, D., Horckmans, M., Megens, R. T. A., 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., ... Soehnlein, O. (2015). Recruitment of classical monocytes can be inhibited by disturbing heteromers of neutrophil HNP1 and platelet CCL5. Science Translational Medicine, 7(317), Article 317ra196. https://doi.org/10.1126/scitranslmed.aad5330

@article{780281ffe5a944d78c6cf5a16e74b0c3,

title = "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, 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.",

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

year = "2015",

month = dec,

day = "9",

doi = "10.1126/scitranslmed.aad5330",

language = "English",

volume = "7",

journal = "Science Translational Medicine",

issn = "1946-6234",

publisher = "American Association for the Advancement of Science",

number = "317",

}

Alard, J-E, Ortega-Gomez, A, Wichapong, K, Bongiovanni, D, Horckmans, M, Megens, RTA, 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, C, Hackeng, TM, Steffens, S, Kupatt, C, Nicolaes, GAF , Weber, C & Soehnlein, O 2015, 'Recruitment of classical monocytes can be inhibited by disturbing heteromers of neutrophil HNP1 and platelet CCL5', Science Translational Medicine, vol. 7, no. 317, 317ra196. https://doi.org/10.1126/scitranslmed.aad5330

TY - JOUR

T1 - Recruitment of classical monocytes can be inhibited by disturbing heteromers of neutrophil HNP1 and platelet CCL5

AU - Alard, Jean-Eric

AU - Ortega-Gomez, Almudena

AU - Wichapong, Kanin

AU - Bongiovanni, Dario

AU - Horckmans, Michael

AU - Megens, Remco T. A.

AU - Leoni, Giovanna

AU - Ferraro, Bartolo

AU - Rossaint, Jan

AU - Paulin, Nicole

AU - Ng, Judy

AU - Ippel, Hans

AU - Suylen, Dennis

AU - Hinkel, Rabea

AU - Blanchet, Xavier

AU - Gaillard, Fanny

AU - D'Amico, Michele

AU - von Hundelshausen, Phillipp

AU - Zarbock, Alexander

AU - Scheiermann, Christoph

AU - Hackeng, Tilman M.

AU - Steffens, Sabine

AU - Kupatt, Christian

AU - Nicolaes, Gerry A. F.

AU - Weber, Christian

AU - Soehnlein, Oliver

PY - 2015/12/9

Y1 - 2015/12/9

N2 - 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.

AB - 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.

U2 - 10.1126/scitranslmed.aad5330

DO - 10.1126/scitranslmed.aad5330

M3 - Article

C2 - 26659570

SN - 1946-6234

VL - 7

JO - Science Translational Medicine

JF - Science Translational Medicine

IS - 317

M1 - 317ra196

ER -

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

Abstract

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