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

Research output: Contribution to journalArticlepeer-review

88 Citations (Scopus)
97 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 languageEnglish
Article number1523
Pages (from-to)1-15
Number of pages15
JournalNature Communications
Volume9
Issue number1
Early online date18 Apr 2018
DOIs
Publication statusPublished - 18 Apr 2018

Fingerprint

Dive into the research topics of 'Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation'. Together they form a unique fingerprint.

Cite this