{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T03:37:13Z","timestamp":1769571433507,"version":"3.49.0"},"reference-count":0,"publisher":"American Society of Hematology","license":[{"start":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T00:00:00Z","timestamp":1680652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Platelets are first responders in thrombosis and hemostasis, but also central players in inflammation. Compared to platelets recruited to thrombi, immune-responsive platelets use distinct effector functions including Arp2\/3-dependent migration along adhesive substrate gradients (haptotaxis), which prevents inflammatory bleeding and contributes to host defense. How platelet migration in this context is regulated on a cellular level is incompletely understood. Here, we use time-resolved morphodynamic profiling of individual platelets to show that migration, in contrast to clot retraction, requires anisotropic myosin IIa-activity at the platelet rear which is preceded by polarized actin polymerization at the front to initiate and maintain migration. Polarization of migrating platelets is coordinated by integrin GPIIb-dependent outside-in signaling via G\u03b113 to trigger tyrosine kinase c-Src\/14-3-3\u03b6-dependent lamellipodium formation and functions independent of soluble agonists or chemotactic signals. Inhibitors of this signaling cascade, including the clinically employed ABL\/c-Src inhibitor dasatinib, interfere predominantly with the migratory capacity of platelets, without major impairment of classical platelet functions. In murine inflammation models, this translates to reduced migration of platelets visualized by 4D intravital microscopy, resulting in increased inflammation-associated hemorrhage in acute lung injury. Finally, platelets isolated from dasatinib-treated leukemia patients prone to clinically relevant hemorrhage exhibit prominent migration defects, while other platelet functions are only partially affected. In summary, we define a distinct signaling pathway essential for migration, and provide novel mechanistic insights explaining dasatinib-related platelet dysfunction and bleeding.<\/jats:p>","DOI":"10.1182\/blood.2022019210","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T20:12:37Z","timestamp":1680725557000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":5,"title":["Mechanosensing via a GpIIb\/Src\/14-3-3\u03b6 axis critically regulates platelet migration in vascular inflammation"],"prefix":"10.1182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1750-3395","authenticated-orcid":false,"given":"Rainer","family":"Kaiser","sequence":"first","affiliation":[{"name":"Department of Medicine I, University Hospital, LMU Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1976-4102","authenticated-orcid":false,"given":"Afra","family":"Anjum","sequence":"additional","affiliation":[{"name":"Department of Medicine I, University Hospital, LMU Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa Maria","family":"Kammerer","sequence":"additional","affiliation":[{"name":"Department of Medicine I, University Hospital, LMU Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quentin","family":"Loew","sequence":"additional","affiliation":[{"name":"Department of Medicine I, University Hospital, LMU Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastassia","family":"Akhalkatsi","sequence":"additional","affiliation":[{"name":"Department of Medicine I, University Hospital, LMU Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dario","family":"Rossaro","sequence":"additional","affiliation":[{"name":"Department of Medicine I, University Hospital, LMU Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raphael","family":"Escaig","sequence":"additional","affiliation":[{"name":"Department of Medicine I, University Hospital, LMU Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Augustin","family":"Droste zu Senden","sequence":"additional","affiliation":[{"name":"Department of Medicine I, University Hospital, LMU Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Raude","sequence":"additional","affiliation":[{"name":"Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, Klinikum der Universit\u00e4t, Ludwig-Maximilians-Universit\u00e4t, Mun, M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Gold","sequence":"additional","affiliation":[{"name":"University Hospital, LMU Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4040-650X","authenticated-orcid":false,"given":"Kami","family":"Pekayvaz","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, Klinikum der Universit\u00e4t, Ludwig-Maximilians-Universit\u00e4t, Mun, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Brocker","sequence":"additional","affiliation":[{"name":"Institute for Immunology, M\u00fcnchen, Alaska, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9928-4132","authenticated-orcid":false,"given":"Jan","family":"Kranich","sequence":"additional","affiliation":[{"name":"Institute for Immunology, LMU Munich, Planegg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian Walter","family":"Holch","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik III, University Hospital Ludwig-Maximilian University, Munich, Germany, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5139-4957","authenticated-orcid":false,"given":"Karsten","family":"Spiekermann","sequence":"additional","affiliation":[{"name":"University Hospital Munich (LMU), Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffen","family":"Massberg","sequence":"additional","affiliation":[{"name":"Klinikum der Universit\u00e4t M\u00fcnchen, Muenchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6120-3723","authenticated-orcid":false,"given":"Florian","family":"Gaertner","sequence":"additional","affiliation":[{"name":"Klinikum der Universit\u00e4t M\u00fcnchen, M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0776-5885","authenticated-orcid":false,"given":"Leo","family":"Nicolai","sequence":"additional","affiliation":[{"name":"University Hospital, LMU Munich, Munich, 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