Resolution of sickle cell disease–associated inflammation and tissue damage with 17R-resolvin D1
Year: 2018
Type: article
Abstract: Resolvins (Rvs), endogenous lipid mediators, play a key role in the resolution of inflammation. Sickle cell disease (SCD), a genetic disorder of hemoglobin, is characterized by inflammatory and vaso-occlusive pathologies. We document altered proresolving events following hypoxia/reperfusion in humanized SCD mice. We demonstrate novel protective actions of 17R-resolvin D1 (17R-RvD1; 7S, 8R, 17R-trihydroxy-4Z, 9E, 11E, 13Z, 15E, 19Z-docosahexaenoic acid) in reducing ex vivo human SCD blood leukocyte recruitment by microvascular endothelial cells and in vivo neutrophil adhesion and transmigration. In SCD mice exposed to hypoxia/reoxygenation, oral administration of 17R-RvD1 reduces systemic/local inflammation and vascular dysfunction in lung and kidney. The mechanism of action of 17R-RvD1 involves (1) enhancement of SCD erythrocytes and polymorphonuclear leukocyte efferocytosis, (2) blunting of NF-κB activation, and (3) a reduction in inflammatory cytokines, vascular activation markers, and E-selectin expression. Thus, 17R-RvD1 might represent a new therapeutic strategy for the inflammatory vasculopathy of SCD.
Source: Blood
Authors: Alessandro Matte, Antonio Recchiuti, Enrica Federti, Bérengère Koehl, Thomas Mintz, Wassim El Nemer, Pierre-Louis Tharaux, Valentine Brousse, Immacolata Andolfo, Alessia Lamolinara, Olga Weinberg, Angela Siciliano, Paul C. Norris, Ian R. Riley, Achille Iolascon, Charles N. Serhan, Carlo Brugnara, Lucia De Franceschi
Institutions: University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, University of Chieti-Pescara, Inserm, Sorbonne Paris Cité, Biologie intégrée du globule rouge et de l'Erythropoïèse, Université Paris Diderot, Paris Cardiovascular Research Center, Université Paris Descartes, Hôpital Necker-Enfants Malades, Assistance Publique – Hôpitaux de Paris, CEINGE Biotecnologie Avanzate Franco Salvatore (Italy), University of Naples Federico II, Boston Children's Hospital, Harvard University, Brigham and Women's Hospital
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2900408930