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cyclo rgdfk-biotin [arg-gly-asp-d-phe-lys /applications/research-applications/multicolor-flow-cytometry/platelet-activation nature portfolio privacy policy writing—editing homogeneous chemokine solutions klinikum der ludwig-maximilians-universität pll-g-peg-biotin-functionalized coverslips thermo fisher scientific reporting summary advertising wasp-family verprolin-homologous protein ten-µm-thick lung cryo-slices open-source platform il-4r/gpib-tg mice social media open chamber assay pf4-cre-negative arpc2fl/fl cytoskeleton–integrin–substrate linkage overcomes negative pf4cre-arpc2fl/fl mice anti-mouse p34-arc/arpc2 anna-kristina marel arg-gly-asp reprints phase-contrast/difference interference contrast mild intra-alveolar bleedings author information authors wiskott–aldrich syndrome protein nature 213 nature 213 nature 402 nature middle biotin–avidin bond ruptures murine bernard-soulier syndrome european research council ludwig-maximilians-universität munich anti-mouse α-sma supplementary movie 1 supplementary movie 2 supplementary movie 3 supplementary movie 4 supplementary movie 5 supplementary movie 6 supplementary movie 7 conditional pf4cre+/− cyfip1fl/fl rac1-mapk–dependent integrin additional arp2/3 inhibition pf4-cre-negative control animals representative f-actin-stained platelet

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         headline:Vascular surveillance by haptotactic blood platelets in inflammation and infection
         description: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. Breakdown of vascular barriers is a major complication of inflammatory diseases. However, the mechanisms underlying platelet recruitment to inflammatory micro-environments remains unclear. Here, the authors identify haptotaxis as a key effector function of immune-responsive platelets
         datePublished:2020-11-13T00:00:00Z
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      headline:Vascular surveillance by haptotactic blood platelets in inflammation and infection
      description: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. Breakdown of vascular barriers is a major complication of inflammatory diseases. However, the mechanisms underlying platelet recruitment to inflammatory micro-environments remains unclear. Here, the authors identify haptotaxis as a key effector function of immune-responsive platelets
      datePublished:2020-11-13T00:00:00Z
      dateModified:2022-08-08T00:00:00Z
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         Actin
         Acute inflammation
         Cell migration
         Platelets
         Science
         Humanities and Social Sciences
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            name:Partner Site Munich Heart Alliance
            address:
               name:DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
               type:PostalAddress
            type:Organization
      name:Vanessa Zheden
      affiliation:
            name:Institute of Science and Technology (IST) Austria
            address:
               name:Institute of Science and Technology (IST) Austria, Klosterneuburg, Austria
               type:PostalAddress
            type:Organization
      name:Markus Bender
      url:http://orcid.org/0000-0002-2381-116X
      affiliation:
            name:University Hospital and Rudolf Virchow Center
            address:
               name:Institute of Experimental Biomedicine I, University Hospital and Rudolf Virchow Center, Würzburg, Germany
               type:PostalAddress
            type:Organization
      name:Rong Li
      url:http://orcid.org/0000-0002-2428-6061
      affiliation:
            name:Johns Hopkins University School of Medicine
            address:
               name:Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, USA
               type:PostalAddress
            type:Organization
      name:Steffen Massberg
      url:http://orcid.org/0000-0001-7387-3986
      affiliation:
            name:Klinikum der Ludwig-Maximilians-Universität
            address:
               name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
               type:PostalAddress
            type:Organization
            name:Partner Site Munich Heart Alliance
            address:
               name:DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Florian Gaertner
      url:http://orcid.org/0000-0001-6120-3723
      affiliation:
            name:Partner Site Munich Heart Alliance
            address:
               name:DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
               type:PostalAddress
            type:Organization
            name:Institute of Science and Technology (IST) Austria
            address:
               name:Institute of Science and Technology (IST) Austria, Klosterneuburg, Austria
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:Ludwig-Maximilians-Universität, Munich, Germany
      name:Ludwig-Maximilians-Universität, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:Walter-Brendel-Centre of Experimental Medicine, University Hospital, München, Germany
      name:Institute of Cardiovascular Physiology and Pathophysiology, Biomedical Center, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:Department of Otorhinolarynology, Ludwig-Maximilians-Universität Munich, Munich, Germany
      name:Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, USA
      name:Department of Otorhinolarynology, Ludwig-Maximilians-Universität Munich, Munich, Germany
      name:Walter-Brendel-Centre of Experimental Medicine, University Hospital, München, Germany
      name:Institute of Cardiovascular Physiology and Pathophysiology, Biomedical Center, Munich, Germany
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
      name:Institute of Science and Technology (IST) Austria, Klosterneuburg, Austria
      name:Institute of Experimental Biomedicine I, University Hospital and Rudolf Virchow Center, Würzburg, Germany
      name:Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, USA
      name:Medizinische Klinik und Poliklinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
      name:DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
      name:DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
      name:Institute of Science and Technology (IST) Austria, Klosterneuburg, Austria

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