Patrolling monocytes scavenge endothelial-adherent sickle RBCs: A novel mechanism of inhibition of vaso-occlusion in SCD

Yunfeng Liu, Hui Zhong, Weili Bao, Avital Mendelson, Xiuli An, Patricia Shi, Stella T. Chou, Deepa Manwani, Karina Yazdanbakhsh

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Painful vaso-occlusive crisis (VOC) is the most common complication of sickle cell disease (SCD). Increasing evidence suggests that vaso-occlusion is initiated by increased adherence of sickle red blood cells (RBCs) to the vascular endothelium. Thus, the mechanisms that remove endothelial-attached sickle RBCs from the microvasculature are expected to be critical for optimal blood flow and prevention of VOC in SCD. We hypothesized that patrolling monocytes (PMos), which protect against vascular damage by scavenging cellular debris, could remove endothelial-adherent sickle RBCs and ameliorate VOC in SCD. We detected RBC (GPA1)-engulfed material in circulating PMos of patients with SCD, and their frequency was further increased during acute crisis. RBC uptake by PMos was specific to endothelial-attached sickle, but not control, RBCs and occurred mostly through ICAM-1, CD11a, and CD18. Heme oxygenase 1 induction, by counteracting the cytotoxic effects of engulfed RBC breakdown products, increased PMo viability. In addition, transfusions, by lowering sickle RBC uptake, improved PMo survival. Selective depletion of PMos in Townes sickle mice exacerbated vascular stasis and tissue damage, whereas treatment with muramyl dipeptide (NOD2 ligand), which increases PMo mass, reduced stasis and SCD associated organ damage. Altogether, these data demonstrate a novel mechanism for removal of endothelial attached sickle RBCs mediated by PMos that can protect against VOC pathogenesis, further supporting PMos as a promising therapeutic target in SCD VOC.

Original languageEnglish (US)
Pages (from-to)579-590
Number of pages12
JournalBlood
Volume134
Issue number7
DOIs
StatePublished - Aug 15 2019

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Liu, Y., Zhong, H., Bao, W., Mendelson, A., An, X., Shi, P., Chou, S. T., Manwani, D., & Yazdanbakhsh, K. (2019). Patrolling monocytes scavenge endothelial-adherent sickle RBCs: A novel mechanism of inhibition of vaso-occlusion in SCD. Blood, 134(7), 579-590. https://doi.org/10.1182/blood.2019000172