# Patrolling Monocytes in Sickle Pain Crisis and following Transfusion

> **NIH NIH R01** · NEW YORK BLOOD CENTER · 2020 · $445,000

## Abstract

Patrolling Monocytes in Sickle Pain Crisis and following Transfusion
Abstract
Patients with sickle cell disease (SCD) suffer from intravascular hemolysis associated with vascular injury and
dysfunction. Painful vaso-occlusive crisis (VOC) involving increased attachment of sickle erythrocytes and
activated leukocytes to damaged vascular endothelium is also a hallmark of SCD. Transfusion lowers sickle
(hemoglobin (Hb S)-containing) RBCs mass, although its use for VOC remains controversial. In SCD, 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 with anti-cytotoxic and anti-
inflammatory properties. We have found that patients with SCD have a novel subset of patrolling monocytes
expressing very high levels of HO-1 (HO-1hi) which are decreased in numbers in patients who had a recent
VOC episode. This monocyte subset was responsible for uptake of hemolysis-damaged endothelium as well
as SCD, but not HD RBCs. In mice, increasing their numbers lowered adherent SCD RBC attachment to the
hemolysis-damaged vascular endothelium. In this proposal, we will test the hypothesis that SCD patrolling
monocytes scavenge and remove damaged endothelium and endothelial-attached sickle RBCs, resulting in
HO-1 upregulation and dampening of VOC. We postulate that when HO-1hi patrolling monocytes are limiting,
there is a buildup of vascular damage and increased sickle RBC attachment to the endothelium, which in turn
increases the risk of VOC. We further posit that transfusions improve survival of HO-1hi patrolling monocytes,
enabling them to effectively clear the vasculature from damaged endothelial cells, thereby affording protection
against VOC. To test our hypotheses, we will determine the mechanisms by which patrolling monocytes
protect SCD vasculature (aim 1); in aim 2, we will dissect the role of HO-1 in anti-VOC activity of patrolling
monocytes, and finally in aim 3, we will examine the association of patrolling monocytes and HO-1hi subset
during i) acute VOC and ii) with chronic transfusions. Altogether, we believe that these studies will help
establish the role of HO-1hi patrolling monocytes in VOC pathophysiology, and their potential as a therapeutic
target for VOC.

## Key facts

- **NIH application ID:** 9976576
- **Project number:** 5R01HL145451-02
- **Recipient organization:** NEW YORK BLOOD CENTER
- **Principal Investigator:** Karina Yazdanbakhsh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $445,000
- **Award type:** 5
- **Project period:** 2019-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976576

## Citation

> US National Institutes of Health, RePORTER application 9976576, Patrolling Monocytes in Sickle Pain Crisis and following Transfusion (5R01HL145451-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9976576. Licensed CC0.

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