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A key role for platelet GPVI in neutrophil recruitment, migration, and NETosis in the early stages of acute lung injury.
Burkard, Philipp; Schonhart, Charlotte; Vögtle, Timo; Köhler, David; Tang, Linyan; Johnson, Denise; Hemmen, Katherina; Heinze, Katrin G; Zarbock, Alexander; Hermanns, Heike M; Rosenberger, Peter; Nieswandt, Bernhard.
Afiliación
  • Burkard P; Institute of Experimental Biomedicine, Chair of Experimental Biomedicine I, University Hospital Würzburg, Würzburg, Germany.
  • Schonhart C; Rudolf Virchow Center for Integrative and Translational Bioimaging, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
  • Vögtle T; Institute of Experimental Biomedicine, Chair of Experimental Biomedicine I, University Hospital Würzburg, Würzburg, Germany.
  • Köhler D; Institute of Experimental Biomedicine, Chair of Experimental Biomedicine I, University Hospital Würzburg, Würzburg, Germany.
  • Tang L; Rudolf Virchow Center for Integrative and Translational Bioimaging, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
  • Johnson D; Department of Anesthesiology and Intensive Care Medicine, University Hospital, Tübingen, Germany.
  • Hemmen K; Department of Anesthesiology and Intensive Care Medicine, University Hospital, Tübingen, Germany.
  • Heinze KG; Institute of Experimental Biomedicine, Chair of Experimental Biomedicine I, University Hospital Würzburg, Würzburg, Germany.
  • Zarbock A; Rudolf Virchow Center for Integrative and Translational Bioimaging, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
  • Hermanns HM; Rudolf Virchow Center for Integrative and Translational Bioimaging, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
  • Rosenberger P; Rudolf Virchow Center for Integrative and Translational Bioimaging, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
  • Nieswandt B; Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany.
Blood ; 142(17): 1463-1477, 2023 10 26.
Article en En | MEDLINE | ID: mdl-37441848
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with high morbidity and mortality. Excessive neutrophil infiltration into the pulmonary airspace is the main cause for the acute inflammation and lung injury. Platelets have been implicated in the pathogenesis of ALI/ARDS, but the underlying mechanisms are not fully understood. Here, we show that the immunoreceptor tyrosine-based activation motif-coupled immunoglobulin-like platelet receptor, glycoprotein VI (GPVI), plays a key role in the early phase of pulmonary thrombo-inflammation in a model of lipopolysaccharide (LPS)-induced ALI in mice. In wild-type (WT) control mice, intranasal LPS application triggered severe pulmonary and blood neutrophilia, hypothermia, and increased blood lactate levels. In contrast, GPVI-deficient mice as well as anti-GPVI-treated WT mice were markedly protected from pulmonary and systemic compromises and showed no increased pulmonary bleeding. High-resolution multicolor microscopy of lung sections and intravital confocal microcopy of the ventilated lung revealed that anti-GPVI treatment resulted in less stable platelet interactions with neutrophils and overall reduced platelet-neutrophil complex (PNC) formation. Anti-GPVI treatment also reduced neutrophil crawling and adhesion on endothelial cells, resulting in reduced neutrophil transmigration and alveolar infiltrates. Remarkably, neutrophil activation was also diminished in anti-GPVI-treated animals, associated with strongly reduced formation of PNC clusters and neutrophil extracellular traps (NETs) compared with that in control mice. These results establish GPVI as a key mediator of neutrophil recruitment, PNC formation, and NET formation (ie, NETosis) in experimental ALI. Thus, GPVI inhibition might be a promising strategy to reduce the acute pulmonary inflammation that causes ALI/ARDS.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neumonía / Síndrome de Dificultad Respiratoria / Lesión Pulmonar Aguda Límite: Animals Idioma: En Revista: Blood Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neumonía / Síndrome de Dificultad Respiratoria / Lesión Pulmonar Aguda Límite: Animals Idioma: En Revista: Blood Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos