TY - JOUR
T1 - Resolution of sickle cell disease–associated inflammation and tissue damage with 17R-resolvin D1
AU - Matte, Alessandro
AU - Recchiuti, Antonio
AU - Federti, Enrica
AU - Koehl, Bérengère
AU - Mintz, Thomas
AU - Nemer, Wassim El
AU - Tharaux, Pierre Louis
AU - Brousse, Valentine
AU - Andolfo, Immacolata
AU - Lamolinara, Alessia
AU - Weinberg, Olga
AU - Siciliano, Angela
AU - Norris, Paul C.
AU - Riley, Ian R.
AU - Iolascon, Achille
AU - Serhan, Charles N.
AU - Brugnara, Carlo
AU - De Franceschi, Lucia
N1 - Publisher Copyright:
© 2019 by The American Society of Hematology
PY - 2019/1/17
Y1 - 2019/1/17
N2 - 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-kB 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.
AB - 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-kB 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.
KW - Defective proresolving response to acute vaso-occlusive events characterizes murine SCD
KW - Treatment with 17R-RvD1 reduces inflammation and vascular dysfunction in SCD mice
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U2 - 10.1182/blood-2018-07-865378
DO - 10.1182/blood-2018-07-865378
M3 - Article
C2 - 30404812
AN - SCOPUS:85060167521
SN - 0006-4971
VL - 133
SP - 252
EP - 265
JO - Blood
JF - Blood
IS - 3
ER -