Vascular surveillance by haptotactic blood platelets in inflammation and infection

article Vascular surveillance by haptotactic blood platelets in inflammation and infection published yes Leo Nicolai author Karin Schiefelbein author Silvia Lipsky author Alexander Leunig author Marie Hoffknecht author Kami Pekayvaz author Ben Raude author Charlotte Marx author Andreas Ehrlich author Joachim Pircher author Zhe Zhang author Inas Saleh author Anna-Kristina Marel author Achim Löf author Tobias Petzold author Michael Lorenz author Konstantin Stark author Robert Pick author Gerhild Rosenberger author Ludwig Weckbach author Bernd Uhl author Sheng Xia author Christoph Andreas Reichel author Barbara Walzog author Christian Schulz author Vanessa Zheden author 39C5A68A-F248-11E8-B48F-1D18A9856A870000-0002-9438-4783 Markus Bender author Rong Li author Steffen Massberg author Florian R Gärtner author 397A88EE-F248-11E8-B48F-1D18A9856A870000-0001-6120-3723 MiSi department EM-Fac department Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells project 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. https://research-explorer.ista.ac.at/download/8787/8798/2020_NatureComm_Nicolai.pdf application/pdfno Springer Nature2020 eng Nature Communications 2041-1723 33188196 00059464800001410.1038/s41467-020-19515-0 11 https://doi.org/10.1038/s41467-022-31310-7 Nicolai, Leo, Karin Schiefelbein, Silvia Lipsky, Alexander Leunig, Marie Hoffknecht, Kami Pekayvaz, Ben Raude, et al. “Vascular Surveillance by Haptotactic Blood Platelets in Inflammation and Infection.” Nature Communications. Springer Nature, 2020. <a href="https://doi.org/10.1038/s41467-020-19515-0">https://doi.org/10.1038/s41467-020-19515-0</a>. L. Nicolai et al., “Vascular surveillance by haptotactic blood platelets in inflammation and infection,” Nature Communications, vol. 11. Springer Nature, 2020. L. Nicolai, K. Schiefelbein, S. Lipsky, A. Leunig, M. Hoffknecht, K. Pekayvaz, B. Raude, C. Marx, A. Ehrlich, J. Pircher, Z. Zhang, I. Saleh, A.-K. Marel, A. Löf, T. Petzold, M. Lorenz, K. Stark, R. Pick, G. Rosenberger, L. Weckbach, B. Uhl, S. Xia, C.A. Reichel, B. Walzog, C. Schulz, V. Zheden, M. Bender, R. Li, S. Massberg, F.R. Gärtner, Nature Communications 11 (2020). Nicolai, Leo, et al. “Vascular Surveillance by Haptotactic Blood Platelets in Inflammation and Infection.” Nature Communications, vol. 11, 5778, Springer Nature, 2020, doi:<a href="https://doi.org/10.1038/s41467-020-19515-0">10.1038/s41467-020-19515-0</a>. Nicolai L, Schiefelbein K, Lipsky S, Leunig A, Hoffknecht M, Pekayvaz K, Raude B, Marx C, Ehrlich A, Pircher J, Zhang Z, Saleh I, Marel A-K, Löf A, Petzold T, Lorenz M, Stark K, Pick R, Rosenberger G, Weckbach L, Uhl B, Xia S, Reichel CA, Walzog B, Schulz C, Zheden V, Bender M, Li R, Massberg S, Gärtner FR. 2020. Vascular surveillance by haptotactic blood platelets in inflammation and infection. Nature Communications. 11, 5778. Nicolai, L., Schiefelbein, K., Lipsky, S., Leunig, A., Hoffknecht, M., Pekayvaz, K., … Gärtner, F. R. (2020). Vascular surveillance by haptotactic blood platelets in inflammation and infection. Nature Communications. Springer Nature. <a href="https://doi.org/10.1038/s41467-020-19515-0">https://doi.org/10.1038/s41467-020-19515-0</a> Nicolai L, Schiefelbein K, Lipsky S, et al. Vascular surveillance by haptotactic blood platelets in inflammation and infection. Nature Communications. 2020;11. doi:<a href="https://doi.org/10.1038/s41467-020-19515-0">10.1038/s41467-020-19515-0</a> 87872020-11-22T23:01:23Z2026-04-02T11:48:21Z