HO-1hipatrolling monocytes protect against vaso-occlusion in sickle cell disease
Publication Date
2018
Journal Title
Blood
Abstract
© 2018 by The American Society of Hematology. 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 patrolling monocytes protect SCD vasculature from ongoing hemolytic insult and vaso-occlusion. We found that a mean 37% of patrolling monocytes from SCD patients express very high levels of HO-1 (HO-1hi) vs 6% in healthy controls and demonstrated that HO-1hiexpression was dependent on uptake of heme-exposed endothelium. SCD patients with a recent VOC episode had lower numbers of HO-1hipatrolling monocytes. Heme-mediated vaso-occlusion by mouse SCD red blood cells was exacerbated in mice lacking patrolling monocytes, and reversed following transfer of patrolling monocytes. Altogether, these data indicate that SCD patrolling monocytes remove hemolysis-damaged endothelial cells, resulting in HO-1 upregulation and dampening of VOC, and that perturbation in patrolling monocyte numbers resulting in lower numbers of HO-1hipatrolling monocyte may predispose SCD patients to VOC. These data suggest that HO-1hipatrolling monocytes are key players in VOC pathophysiology and have potential as therapeutic targets for VOC.
Volume Number
131
Issue Number
14
Pages
1600 - 1610
Document Type
Article
Status
Faculty
Facility
School of Medicine
Primary Department
Cardiology
PMID
DOI
10.1182/blood-2017-12-819870