Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation

Joachim Pircher; Thomas Czermak; Andreas Ehrlich; Clemens Eberle; Erik Gaitzsch; Andreas Margraf; Jochen Grommes; Prakash Saha; Anna Titova; Hellen Ishikawa-Ankerhold; Konstantin Stark; Tobias Petzold; Thomas Stocker; Ludwig T. Weckbach; Julia Novotny; Markus Sperandio; Bernhard Nieswandt; Alberto Smith; Hanna Mannell; Barbara Walzog; David Horst; Oliver Soehnlein; Steffen Massberg; Christian Schulz

doi:10.1038/s41467-018-03925-2

Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation

Joachim Pircher, Thomas Czermak, Andreas Ehrlich, Clemens Eberle, Erik Gaitzsch, Andreas Margraf, Jochen Grommes, Prakash Saha, Anna Titova, Hellen Ishikawa-Ankerhold, Konstantin Stark, Tobias Petzold, Thomas Stocker, Ludwig T. Weckbach, Julia Novotny, Markus Sperandio, Bernhard Nieswandt, Alberto Smith, Hanna Mannell, Barbara WalzogDavid Horst, Oliver Soehnlein, Steffen Massberg, Christian Schulz^*

^*Corresponding author for this work

Vascular Risk & Surgery

Research output: Contribution to journal › Article › peer-review

96 Citations (Scopus)

117 Downloads (Pure)

Abstract

Leukocyte-released antimicrobial peptides contribute to pathogen elimination and activation of the immune system. Their role in thrombosis is incompletely understood. Here we show that the cathelicidin LL-37 is abundant in thrombi from patients with acute myocardial infarction. Its mouse homologue, CRAMP, is present in mouse arterial thrombi following vascular injury, and derives mainly from circulating neutrophils. Absence of hematopoietic CRAMP in bone marrow chimeric mice reduces platelet recruitment and thrombus formation. Both LL-37 and CRAMP induce platelet activation in vitro by involving glycoprotein VI receptor with downstream signaling through protein tyrosine kinases Src/Syk and phospholipase C. In addition to acute thrombosis, LL-37/CRAMP-dependent platelet activation fosters platelet-neutrophil interactions in other inflammatory conditions by modulating the recruitment and extravasation of neutrophils into tissues. Absence of CRAMP abrogates acid-induced lung injury, a mouse pneumonia model that is dependent on platelet-neutrophil interactions. We suggest that LL-37/CRAMP represents an important mediator of platelet activation and thrombo-inflammation.

Original language	English
Article number	1523
Pages (from-to)	1-15
Number of pages	15
Journal	Nature Communications
Volume	9
Issue number	1
Early online date	18 Apr 2018
DOIs	https://doi.org/10.1038/s41467-018-03925-2
Publication status	Published - 18 Apr 2018

Access to Document

10.1038/s41467-018-03925-2Licence: CC BY

Cathelicidins prime platelets_SAHA_Publishedonline18April2018_GOLD VoR (CC BY)Final published version, 3.18 MBLicence: CC BY

Cite this

Pircher, J., Czermak, T., Ehrlich, A., Eberle, C., Gaitzsch, E., Margraf, A., Grommes, J., Saha, P., Titova, A., Ishikawa-Ankerhold, H., Stark, K., Petzold, T., Stocker, T., Weckbach, L. T., Novotny, J., Sperandio, M., Nieswandt, B., Smith, A., Mannell, H., ... Schulz, C. (2018). Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation. Nature Communications, 9(1), 1-15. Article 1523. https://doi.org/10.1038/s41467-018-03925-2

@article{4ea8ce9934c64d9cb654e684623da6bd,

title = "Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation",

abstract = "Leukocyte-released antimicrobial peptides contribute to pathogen elimination and activation of the immune system. Their role in thrombosis is incompletely understood. Here we show that the cathelicidin LL-37 is abundant in thrombi from patients with acute myocardial infarction. Its mouse homologue, CRAMP, is present in mouse arterial thrombi following vascular injury, and derives mainly from circulating neutrophils. Absence of hematopoietic CRAMP in bone marrow chimeric mice reduces platelet recruitment and thrombus formation. Both LL-37 and CRAMP induce platelet activation in vitro by involving glycoprotein VI receptor with downstream signaling through protein tyrosine kinases Src/Syk and phospholipase C. In addition to acute thrombosis, LL-37/CRAMP-dependent platelet activation fosters platelet-neutrophil interactions in other inflammatory conditions by modulating the recruitment and extravasation of neutrophils into tissues. Absence of CRAMP abrogates acid-induced lung injury, a mouse pneumonia model that is dependent on platelet-neutrophil interactions. We suggest that LL-37/CRAMP represents an important mediator of platelet activation and thrombo-inflammation.",

author = "Joachim Pircher and Thomas Czermak and Andreas Ehrlich and Clemens Eberle and Erik Gaitzsch and Andreas Margraf and Jochen Grommes and Prakash Saha and Anna Titova and Hellen Ishikawa-Ankerhold and Konstantin Stark and Tobias Petzold and Thomas Stocker and Weckbach, {Ludwig T.} and Julia Novotny and Markus Sperandio and Bernhard Nieswandt and Alberto Smith and Hanna Mannell and Barbara Walzog and David Horst and Oliver Soehnlein and Steffen Massberg and Christian Schulz",

year = "2018",

month = apr,

day = "18",

doi = "10.1038/s41467-018-03925-2",

language = "English",

volume = "9",

pages = "1--15",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Pircher, J, Czermak, T, Ehrlich, A, Eberle, C, Gaitzsch, E, Margraf, A, Grommes, J, Saha, P, Titova, A, Ishikawa-Ankerhold, H, Stark, K, Petzold, T, Stocker, T, Weckbach, LT, Novotny, J, Sperandio, M, Nieswandt, B, Smith, A, Mannell, H, Walzog, B, Horst, D, Soehnlein, O, Massberg, S & Schulz, C 2018, 'Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation', Nature Communications, vol. 9, no. 1, 1523, pp. 1-15. https://doi.org/10.1038/s41467-018-03925-2

TY - JOUR

T1 - Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation

AU - Pircher, Joachim

AU - Czermak, Thomas

AU - Ehrlich, Andreas

AU - Eberle, Clemens

AU - Gaitzsch, Erik

AU - Margraf, Andreas

AU - Grommes, Jochen

AU - Saha, Prakash

AU - Titova, Anna

AU - Ishikawa-Ankerhold, Hellen

AU - Stark, Konstantin

AU - Petzold, Tobias

AU - Stocker, Thomas

AU - Weckbach, Ludwig T.

AU - Novotny, Julia

AU - Sperandio, Markus

AU - Nieswandt, Bernhard

AU - Smith, Alberto

AU - Mannell, Hanna

AU - Walzog, Barbara

AU - Horst, David

AU - Soehnlein, Oliver

AU - Massberg, Steffen

AU - Schulz, Christian

PY - 2018/4/18

Y1 - 2018/4/18

N2 - Leukocyte-released antimicrobial peptides contribute to pathogen elimination and activation of the immune system. Their role in thrombosis is incompletely understood. Here we show that the cathelicidin LL-37 is abundant in thrombi from patients with acute myocardial infarction. Its mouse homologue, CRAMP, is present in mouse arterial thrombi following vascular injury, and derives mainly from circulating neutrophils. Absence of hematopoietic CRAMP in bone marrow chimeric mice reduces platelet recruitment and thrombus formation. Both LL-37 and CRAMP induce platelet activation in vitro by involving glycoprotein VI receptor with downstream signaling through protein tyrosine kinases Src/Syk and phospholipase C. In addition to acute thrombosis, LL-37/CRAMP-dependent platelet activation fosters platelet-neutrophil interactions in other inflammatory conditions by modulating the recruitment and extravasation of neutrophils into tissues. Absence of CRAMP abrogates acid-induced lung injury, a mouse pneumonia model that is dependent on platelet-neutrophil interactions. We suggest that LL-37/CRAMP represents an important mediator of platelet activation and thrombo-inflammation.

AB - Leukocyte-released antimicrobial peptides contribute to pathogen elimination and activation of the immune system. Their role in thrombosis is incompletely understood. Here we show that the cathelicidin LL-37 is abundant in thrombi from patients with acute myocardial infarction. Its mouse homologue, CRAMP, is present in mouse arterial thrombi following vascular injury, and derives mainly from circulating neutrophils. Absence of hematopoietic CRAMP in bone marrow chimeric mice reduces platelet recruitment and thrombus formation. Both LL-37 and CRAMP induce platelet activation in vitro by involving glycoprotein VI receptor with downstream signaling through protein tyrosine kinases Src/Syk and phospholipase C. In addition to acute thrombosis, LL-37/CRAMP-dependent platelet activation fosters platelet-neutrophil interactions in other inflammatory conditions by modulating the recruitment and extravasation of neutrophils into tissues. Absence of CRAMP abrogates acid-induced lung injury, a mouse pneumonia model that is dependent on platelet-neutrophil interactions. We suggest that LL-37/CRAMP represents an important mediator of platelet activation and thrombo-inflammation.

UR - http://www.scopus.com/inward/record.url?scp=85045626527&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-03925-2

DO - 10.1038/s41467-018-03925-2

M3 - Article

AN - SCOPUS:85045626527

SN - 2041-1723

VL - 9

SP - 1

EP - 15

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1523

ER -

Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation

Abstract

Access to Document

Other files and links

Fingerprint

Cite this