HO-1 hi patrolling monocytes protect against vaso-occlusion in sickle cell disease

Yunfeng Liu, Fangmiao Jing, Woelsung Yi, Avital Mendelson, Patricia Shi, Ronald Walsh, David F. Friedman, Caterina Minniti, Deepa Manwani, Stella T. Chou, Karina Yazdanbakhsh

Research output: Contribution to journalArticle

12 Scopus citations

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 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-1 hi ) vs 6% in healthy controls and demonstrated that HO-1 hi expression was dependent on uptake of heme-exposed endothelium. SCD patients with a recent VOC episode had lower numbers of HO-1 hi patrolling 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-1 hi patrolling monocyte may predispose SCD patients to VOC. These data suggest that HO-1 hi patrolling monocytes are key players in VOC pathophysiology and have potential as therapeutic targets for VOC.

Original languageEnglish (US)
Pages (from-to)1600-1610
Number of pages11
JournalBlood
Volume131
Issue number14
DOIs
StatePublished - Apr 5 2018

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Liu, Y., Jing, F., Yi, W., Mendelson, A., Shi, P., Walsh, R., Friedman, D. F., Minniti, C., Manwani, D., Chou, S. T., & Yazdanbakhsh, K. (2018). HO-1 hi patrolling monocytes protect against vaso-occlusion in sickle cell disease Blood, 131(14), 1600-1610. https://doi.org/10.1182/blood-2017-12-819870