Vascular surveillance by haptotactic blood platelets in inflammation and infection

Leo Nicolai, Karin Schiefelbein, Silvia Lipsky, Alexander Leunig, Marie Hoffknecht, Kami Pekayvaz, Ben Raude, Charlotte Marx, Andreas Ehrlich, Joachim Pircher, Zhe Zhang, Inas Saleh, Anna Kristina Marel, Achim Löf, Tobias Petzold, Michael Lorenz, Konstantin Stark, Robert Pick, Gerhild Rosenberger, Ludwig WeckbachBernd Uhl, Sheng Xia, Christoph Andreas Reichel, Barbara Walzog, Christian Schulz, Vanessa Zheden, Markus Bender, Rong Li, Steffen Massberg, Florian Gaertner

Research output: Contribution to journalArticlepeer-review

Abstract

Breakdown of vascular barriers is a major complication of inflammatory diseases. Anucleate platelets form blood-clots during thrombosis, but also play a crucial role in inflammation. While spatio-temporal dynamics of clot formation are well characterized, the cell-biological mechanisms of platelet recruitment to inflammatory micro-environments remain incompletely understood. Here we identify Arp2/3-dependent lamellipodia formation as a prominent morphological feature of immune-responsive platelets. Platelets use lamellipodia to scan for fibrin(ogen) deposited on the inflamed vasculature and to directionally spread, to polarize and to govern haptotactic migration along gradients of the adhesive ligand. Platelet-specific abrogation of Arp2/3 interferes with haptotactic repositioning of platelets to microlesions, thus impairing vascular sealing and provoking inflammatory microbleeding. During infection, haptotaxis promotes capture of bacteria and prevents hematogenic dissemination, rendering platelets gate-keepers of the inflamed microvasculature. Consequently, these findings identify haptotaxis as a key effector function of immune-responsive platelets.

Original languageEnglish (US)
Article number5778
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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