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 and Christian Schulz ()
Additional contact information
Joachim Pircher: Klinikum der Universität München, Ludwig-Maximilians-University
Thomas Czermak: Klinikum der Universität München, Ludwig-Maximilians-University
Andreas Ehrlich: Klinikum der Universität München, Ludwig-Maximilians-University
Clemens Eberle: Klinikum der Universität München, Ludwig-Maximilians-University
Erik Gaitzsch: Ludwig-Maximilians-University
Andreas Margraf: Ludwig-Maximilians-University
Jochen Grommes: Ludwig-Maximilians-University
Prakash Saha: King’s College London, St. Thomas’ Hospital
Anna Titova: Klinikum der Universität München, Ludwig-Maximilians-University
Hellen Ishikawa-Ankerhold: Klinikum der Universität München, Ludwig-Maximilians-University
Konstantin Stark: Klinikum der Universität München, Ludwig-Maximilians-University
Tobias Petzold: Klinikum der Universität München, Ludwig-Maximilians-University
Thomas Stocker: Klinikum der Universität München, Ludwig-Maximilians-University
Ludwig T Weckbach: Klinikum der Universität München, Ludwig-Maximilians-University
Julia Novotny: Klinikum der Universität München, Ludwig-Maximilians-University
Markus Sperandio: partner site Munich Heart Alliance
Bernhard Nieswandt: University Hospital Würzburg
Alberto Smith: King’s College London, St. Thomas’ Hospital
Hanna Mannell: Ludwig-Maximilians-University
Barbara Walzog: Ludwig-Maximilians-University
David Horst: Ludwig-Maximilians-University
Oliver Soehnlein: partner site Munich Heart Alliance
Steffen Massberg: Klinikum der Universität München, Ludwig-Maximilians-University
Christian Schulz: Klinikum der Universität München, Ludwig-Maximilians-University

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03925-2

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