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

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

Research output: Contribution to journalArticlepeer-review

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-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.

Original languageEnglish (US)
Pages (from-to)252-265
Number of pages14
JournalBlood
Volume133
Issue number3
DOIs
StatePublished - Jan 17 2019
Externally publishedYes

Keywords

  • Defective proresolving response to acute vaso-occlusive events characterizes murine SCD
  • Treatment with 17R-RvD1 reduces inflammation and vascular dysfunction in SCD mice

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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