What is it about?
We have found that blocking endothelin receptors, particularly ETB receptor highly influences neutrophils recruitment under inflammatory conditions in sickle cell disease. We show that human neutrophils display functional ETB receptors leading to increased adhesion to the endothelium. Furthermore, we confirmed that human neutrophils synthesize endothelin-1 that may be involved in the severe and painful Sicklle Cell crises.
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Why is it important?
Patients affected by Sickle Cell Disease are prone to severe vaso-occlusive crises (VOC) but also to infections. Neutrophils are important to protect people from infections. Thus, we need therapies that treat or prevent VOC without impairing the anti-infectious defense.
Perspectives
A role for the ETA-type endothelin receptor has been suspected in Sickle Cell Disease. Meanwhile, This study unravel a potent pro-inflammatory role for the ETB receptor with relevance to the human condition. These results should foster clinical trials using dual ETA and ETB antagonists to optimally treat this severe disease. The paradigm of a pro-inflammatory role for this pathway in other diseases should also be explored.
MD, PhD Pierre-Louis Tharaux
Institut de la Santé et de la Recherche Médicale, Inserm
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This page is a summary of: The endothelin B receptor plays a crucial role in the adhesion of neutrophils to the endothelium in sickle cell disease, Haematologica, April 2017, Ferrata Storti Foundation (Haematologica),
DOI: 10.3324/haematol.2016.156869.
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