Trusted Resources: Evidence & Education
Scientific literature and patient education texts
The endothelin B receptor plays a crucial role in the adhesion of neutrophils to the endothelium in sickle cell disease
source: Haematologica
year: 2017
authors: Koehl B, Nivoit P, El Nemer W, Lenoir O, Hermand P, Pereira C, Brousse V, Guyonnet L, Ghinatti G, Benkerrou M, Colin Y, Le Van Kim C, Tharaux PL
summary/abstract:Although the primary origin of sickle cell disease is a hemoglobin disorder, many types of cells contribute considerably to the pathophysiology of the disease. The adhesion of neutrophils to activated endothelium is critical in the pathophysiology of sickle cell disease and targeting neutrophils and their interactions with endothelium represents an important opportunity for the development of new therapeutics. We focused on endothelin-1, a mediator involved in neutrophil activation and recruitment in tissues, and investigated the involvement of the endothelin receptors in the interaction of neutrophils with endothelial cells. We used fluorescence intravital microscopy analyses of the microcirculation in sickle mice and quantitative microfluidic fluorescence microscopy of human blood. Both experiments on the mouse model and patients indicate that blocking endothelin receptors, particularly ETB receptor, strongly influences neutrophil recruitment under inflammatory conditions in sickle cell disease. We show that human neutrophils have functional ETB receptors with calcium signaling capability, leading to increased adhesion to the endothelium through effects on both endothelial cells and neutrophils. Intact ETB function was found to be required for tumor necrosis factor α-dependent upregulation of CD11b on neutrophils. Furthermore, we confirmed that human neutrophils synthesize endothelin-1, which may be involved in autocrine and paracrine pathophysiological actions. Thus, the endothelin-ETB axis should be considered as a cytokine-like potent pro-inflammatory pathway in sickle cell disease. Blockade of endothelin receptors, including ETB, may provide major benefits for preventing or treating vaso-occlusive crises in sickle cell patients.
organization: Université Sorbonne Paris Cité; Université Paris Diderot, Inserm, INTS; Unité Biologie Intégrée du Globule Rouge; Laboratoire d'Excellence GR-Ex, France; Assistance Publique-Hôpitaux de Paris; Robert Debré Hospital, Reference Centre of Sickle Cell Disease, FranceDOI: 10.3324/haematol.2016.156869
read more full text
+myBinderRelated Content
-
Hemoglobin A1c and Fructosamine Correlate in a Patient With Sickle Cell Disease And Diabetes on Chronic Transfusion ...In patients with sickle cell disease (SC...
-
A Conversation With a Twist: Mental Health and Sickle Cell DiseaseOur goal is to help raise awareness abou...
-
Tricuspid Regurgitant Jet Velocity and Myocardial Tissue Doppler Parameters Predict Mortality in a Cohort of Patient...Sickle cell disease (SCD) is a monogenic...
-
Christiana Care Sickle Cell ProgramChristiana Care is one of the country’...
-
Adulting is especially difficult for youth with special health care needsThere are approximately 4.3 million adol...
-
Statement from FDA Commissioner on agency’s efforts to advance development of gene therapiesOnce just a theory, gene therapies are...
-
Kathryn Hassell, MDDr. Hassell provides inpatient and outpa...
To improve your experience on this site, we use cookies. This includes cookies essential for the basic functioning of our website, cookies for analytics purposes, and cookies enabling us to personalize site content. By clicking on 'Accept' or any content on this site, you agree that cookies can be placed. You may adjust your browser's cookie settings to suit your preferences. More Information
The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.
Powered by
Support for this site is provided by
This platform is made possible through a partnership with the Sickle Cell Disease Association of America, Inc. (SCDAA) and its member organizations. SCDAA's mission is to advocate for people affected by sickle cell conditions and empower community-based organizations to maximize quality of life and raise public consciousness while advancing the search for a universal cure.