Resolution of sickle cell disease-associated inflammation and tissue damage with 17 R -resolvin D1

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 human...

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Published inBlood Vol. 133; no. 3; p. 252
Main Authors Matte, Alessandro, Recchiuti, Antonio, Federti, Enrica, Koehl, Bérengère, Mintz, Thomas, El Nemer, Wassim, Tharaux, Pierre-Louis, Brousse, Valentine, Andolfo, Immacolata, Lamolinara, Alessia, Weinberg, Olga, Siciliano, Angela, Norris, Paul C, Riley, Ian R, Iolascon, Achille, Serhan, Charles N, Brugnara, Carlo, De Franceschi, Lucia
Format Journal Article
LanguageEnglish
Published United States 17.01.2019
Subjects
Anemia, Sickle Cell - complications
Animals
Anti-Inflammatory Agents, Non-Steroidal - administration & dosage
Cytokines - metabolism
Docosahexaenoic Acids - administration & dosage
Humans
Kidney Diseases - etiology
Kidney Diseases - pathology
Kidney Diseases - prevention & control
Mice
Neutrophils - immunology
Neutrophils - metabolism
Neutrophils - pathology
Pneumonia - etiology
Pneumonia - pathology
Pneumonia - prevention & control
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Summary: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 17 -resolvin D1 (17 RvD1; 7 , 8 , 17 -trihydroxy-4 , 9 , 11 , 13 , 15 , 19 -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 17 RvD1 reduces systemic/local inflammation and vascular dysfunction in lung and kidney. The mechanism of action of 17 -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, 17 -RvD1 might represent a new therapeutic strategy for the inflammatory vasculopathy of SCD.
ISSN:1528-0020