2018
DOI: 10.1182/blood-2017-12-819870
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HO-1hi patrolling monocytes protect against vaso-occlusion in sickle cell disease

Abstract: Patients with sickle cell disease (SCD) suffer from intravascular hemolysis associated with vascular injury and dysfunction in mouse models, and painful vaso-occlusive crisis (VOC) involving increased attachment of sickle erythrocytes and activated leukocytes to damaged vascular endothelium. Patrolling monocytes, which normally scavenge damaged cells and debris from the vasculature, express higher levels of anti-inflammatory heme oxygenase 1 (HO-1), a heme degrading enzyme. Here, we show that HO-1-expressing p… Show more

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Cited by 35 publications
(51 citation statements)
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“…A monocyte‐tumor necrosis factor‐endothelial activation axis has recently been described in animal models of SCD, with monocytes generating large amounts of pro‐inflammatory cytokines. A recent study also has shed light on the potential importance of non‐classical “patrolling” monocytes and vaso‐occlusion …”
Section: Discussionmentioning
confidence: 99%
“…A monocyte‐tumor necrosis factor‐endothelial activation axis has recently been described in animal models of SCD, with monocytes generating large amounts of pro‐inflammatory cytokines. A recent study also has shed light on the potential importance of non‐classical “patrolling” monocytes and vaso‐occlusion …”
Section: Discussionmentioning
confidence: 99%
“…Plasma exchange Because free heme and free Hb can have deleterious effects on vasculature, 10,11 plasma exchange may be effective in severe cases of hyperhemolysis 58 and was successfully shown to detoxify heme in patients with acute MOF without DHTR. 59 However, the extracorporeal volume, which can further lower the Hb level, needs to be considered.…”
Section: H T R L I K E L I H O O D L O W I N T E R M E D I a T E H mentioning
confidence: 99%
“…Hyperhemolysis can induce multiorgan failure (MOF) and death, most likely because of damage to the underlying vasculature by released free hemoglobin (Hb) and heme. 10,11 Additional transfusions are frequently prescribed but can worsen hemolysis. Based on retrospective studies, the incidence of severe DHTR is 11.5% to 16% with only ABO and RhD matching and 4% to 7% in patients matched for Rh (D, C, E, c, e) and K (supplemental Table 1, available on the Blood Web site); in an adult cohort, DHTRs represented 4.2% of all causes of death in SCD.…”
Section: Introductionmentioning
confidence: 99%
“…We recently reported that a novel circulating PMo subset expressing very high levels of HO-1 (HO-1 hi ) is present exclusively in SCD patients and that patients with a recent VOC episode have reduced numbers of HO-1 hi PMo. 21 We showed that PMo clear hemolysisdamaged ECs with a concomitant upregulation of HO-1. ICAM-1 and PS expression on ECs was shown to be required for induction of HO-1 hi expression in PMo when cultured with hemolysis-damaged ECs.…”
mentioning
confidence: 75%