Blood: When Platelets Get Out of Control
08/04/2023Acute lung failure is life-threatening - especially if it is accompanied by an excessive immune reaction. Researchers at the University Medical Centre Würzburg have now discovered how this reaction can be suppressed.
One in ten people receiving intensive care develops acute respiratory distress syndrome (ARDS). Most of these respiratory distress syndromes, the mild form of which is also known as ALI (Acute Lung Injury), are caused by pneumonia, but blood poisoning, external injuries, blood cancer and autoimmune diseases or so-called foreign body aspiration can also have a life-threatening effect on lung function.
Common to all causes are inflammatory processes that damage the lung tissue. Despite improved treatment options, the risk of death is high. The therapeutic approaches to combat ARDS are mainly supportive and focus on mechanical ventilation that is gentle on the lungs.
Unstoppable Damage to the Lung Tissue
Even with supposedly effective antibiotics, inflammation often persists and damages the protective barrier of the blood vessels in the lungs, leading to immune-mediated injury to the lung tissue. The main culprits in this damaging process are neutrophil granulocytes. This type of white blood cell actually helps the body to fight infections and heal injuries.
In acute lung failure, the neutrophils penetrate the lung tissue in a multi-stage process and break through the lining of the blood vessels early on in the inflammatory phase. Platelets play a key role in supporting the recruitment and activation of neutrophils.
Platelets Can Drive Acute Inflammatory Processes
Professor Bernhard Nieswandt, Head of the Chair of Experimental Biomedicine I and research group leader at the Rudolf Virchow Centre - Center for Integrative and Translational Bioimaging (RVZ) at the University of Würzburg and Director of the Institute of Experimental Biomedicine at the University Hospital of Würzburg, has been researching the complex functions of platelets for years and has now found an approach to prevent the infiltration of neutrophils into lung tissue.
"The small seedless blood cells can do much more than stop haemorrhages and trigger infarctions, for example trigger inflammatory processes. The mechanism is known as thrombo-inflammation," says Bernhard Nieswandt, describing the functions of platelets, which are continuously formed from megakaryocytes in the bone marrow.
In the latest study published in the journal Blood, Bernhard Nieswandt's team has found a promising target for reducing the acute inflammation that causes ALI/ARDS. The activating platelet receptor glycoprotein VI (GPVI) could play a decisive role in the activation and spread of thrombo-inflammation.
A Promising Point of Attack
"Our data show that the targeted inhibition of GPVI, which is located on the surface of blood platelets, by an antibody significantly reduces the devastating influx of neutrophils into the lung tissue and the resulting tissue damage to the inflamed lung, without increasing the risk of inflammatory haemorrhage," explains Bernhard Nieswandt and summarises: "The results could pave the way for new therapeutic approaches to combat these life-threatening diseases."
Philipp Burkard, scientist at the Würzburg Institute of Experimental Biomedicine and first author of the study, adds: "If we specifically suppress GPVI with an antibody, we can prevent the extent of the excessive immune response, which improves the barrier function of the blood-air barrier and thus also the clinical outcome."
In a further study, the researchers will investigate the effect of a blocking GPVI antibody in a humanised mouse model in which the blood platelets express the human version of GPVI. This will bring them closer to the situation in humans and will further confirm the benefits of anti-GPVI treatment.
This work was funded by the German Research Foundation (project SFB/TR240 and SFB 1525).
Publication
A key role for platelet GPVI in neutrophil recruitment, migration and NETosis in the early stages of acute lung injury: Burkard P, Schonhart C, Vögtle T, Köhler D, Tang L, Johnson D, Hemmen K, Heinze KG, Zarbock A, Hermanns HM, Rosenberger P, Nieswandt B. Blood. 2023 Jul 13 / doi: 10.1182/blood.2023019940. Online ahead of print. PMID: 37441848
Contact
Prof. Dr Bernhard Nieswandt (Rudolf Virchow Centre, University of Würzburg & Head of the Chair of Experimental Biomedicine I, University Hospital Würzburg) Phone: + 49 931 31-80405, bernhard.nieswandt@virchow.uni-wuerzburg.de
Dr Daniela Diefenbacher, Press Office, Rudolf Virchow Center - Center for Integrative and Translational Bioimaging, University of Würzburg, +49 931 31-88631, daniela.diefenbacher@uni-wuerzburg.de
Kirstin Linkamp, Press Office, University Hospital Würzburg, +49 931 201 59 458, Linkamp_K@ukw.de
