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 Weckbach, Bernd Uhl, Sheng Xia, Christoph Andreas Reichel, Barbara Walzog, Christian Schulz, Vanessa Zheden, Markus Bender, Rong Li, Steffen Massberg () and Florian Gaertner ()
Additional contact information
Leo Nicolai: Klinikum der Ludwig-Maximilians-Universität
Karin Schiefelbein: Klinikum der Ludwig-Maximilians-Universität
Silvia Lipsky: Klinikum der Ludwig-Maximilians-Universität
Alexander Leunig: Klinikum der Ludwig-Maximilians-Universität
Marie Hoffknecht: Klinikum der Ludwig-Maximilians-Universität
Kami Pekayvaz: Klinikum der Ludwig-Maximilians-Universität
Ben Raude: Klinikum der Ludwig-Maximilians-Universität
Charlotte Marx: Klinikum der Ludwig-Maximilians-Universität
Andreas Ehrlich: Klinikum der Ludwig-Maximilians-Universität
Joachim Pircher: Klinikum der Ludwig-Maximilians-Universität
Zhe Zhang: Klinikum der Ludwig-Maximilians-Universität
Inas Saleh: Klinikum der Ludwig-Maximilians-Universität
Anna-Kristina Marel: Ludwig-Maximilians-Universität
Achim Löf: Ludwig-Maximilians-Universität
Tobias Petzold: Klinikum der Ludwig-Maximilians-Universität
Michael Lorenz: Klinikum der Ludwig-Maximilians-Universität
Konstantin Stark: Klinikum der Ludwig-Maximilians-Universität
Robert Pick: University Hospital
Gerhild Rosenberger: Klinikum der Ludwig-Maximilians-Universität
Ludwig Weckbach: Klinikum der Ludwig-Maximilians-Universität
Bernd Uhl: Ludwig-Maximilians-Universität Munich
Sheng Xia: Johns Hopkins University School of Medicine
Christoph Andreas Reichel: Ludwig-Maximilians-Universität Munich
Barbara Walzog: University Hospital
Christian Schulz: Klinikum der Ludwig-Maximilians-Universität
Vanessa Zheden: Institute of Science and Technology (IST) Austria
Markus Bender: University Hospital and Rudolf Virchow Center
Rong Li: Johns Hopkins University School of Medicine
Steffen Massberg: Klinikum der Ludwig-Maximilians-Universität
Florian Gaertner: Partner Site Munich Heart Alliance

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19515-0

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