Patrolling monocytes in sickle cell hemolytic conditions

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 a hallmark of 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. Recent data show that patients with SCD have a novel subset of patrolling monocytes expressing very high levels of HO-1 (HO-1 hi) which are decreased in numbers in patients who had a recent VOC episode. This patrolling monocyte subset was responsible for protection of endothelium against sickle RBC stasis in an experimental model. This raises the possibility that patrolling monocytes may also offer protection against vascular endothelium damage in hyperhemolytic conditions in SCD. Résumé Les patients drépanocytaires présentent une hémolyse intravasculaire associée à un effet délétère sur les vaisseaux. Au cours des crises vaso-occlusives (CVO) caractéristiques de la maladie, les GR drépanocytaires et les leucocytes altèrent la paroi des vaisseaux. Les monocytes en circulation ont une expression augmentée de d'hème Oxygénase 1 (HO-1), qui dégrade les débris, avec des caractéristiques anti-inflammatoires. Des données récentes ont montré que les drépanocytaires ont des monocytes circulants avec un taux élevé de HO-1, qui diminue au cours des CVO. Ces monocytes sont responsables, dans un modèle murin, de la protection de l'endothélium vis-à-vis de la stase des globules rouges au cours de la drépanocytose. Ils pourraient aussi jouer un rôle de protection vis-à-vis des effets de l'hyperhémolyse post-transfusionnelle sur l'endothélium vasculaire.

Stratification of βSβ+ Compound Heterozygotes Based on L-Glutamine Administration and RDW: Focusing on Disease Severity

“…Accordingly, in the current study, the high-RDW group was associated with a slight increase in some inflammation markers, like leukocyte counts, C-reactive protein, and immunoglobulins. Monocytes, which have been reported to be elevated in SCD and were also increased in the currently presented high-RDW subgroup, are often modulated into inflammatory monocytes [43], which intensifies the production of pro-inflammatory molecules in SCD. Inflammation and the altered macrophages can alter both erythropoiesis and erythrocyte survival, which can lead to a mixed RBC population in circulation, mirrored by RDW [44].…”

Role of Macrophages in Sickle Cell Disease Erythrophagocytosis and Erythropoiesis

“…Monocyte counts have been reported as significantly elevated in patients with SCA compared with healthy individuals, and indeed, they are reduced by hydroxyurea therapy [ 54 ]. Depletion of the non-classical patrolling monocyte subset (CD14 dim CD16 + ) has been reported in SCD [ 58 ], which is possibly due to their modulation into inflammatory monocytes or their destruction following the scavenging of endothelial-adherent sickle RBCs [ 59 ]. Although heme-induced splenic macrophage expansion together with dendritic cell depletion has been reported in mice with SCD [ 23 ], as well as Nrf2-dependent macrophage hypercellularity during stress erythropoiesis (a feature of SCD) [ 60 , 61 ], it is not clear whether leukocytosis and the changes in monocyte profiles described in SCD contribute to drive the differentiation of macrophages and their role in erythropoiesis.…”

Hemolysis dictates monocyte differentiation via two distinct pathways in sickle cell disease vaso-occlusion

“…Sickle cell disease (SCD) is characterized by hemolytic anemia and painful vaso-occlusive crises (VOC), caused by increased adherence of sickle RBCs to the underlying activated vascular endothelium (1,2) Accumulating evidence highlights the pivotal role of the mononuclear phagocyte system, encompassing blood monocytes, spleen red pulp macrophages, and liver Kupffer cells, in erythrophagocytosis of sickle RBCs and in the clearance of hemolytic byproducts in SCD (3)(4)(5)(6)(7)(8)(9)(10)(11). Our recent findings demonstrate that, a subset of blood monocytes, known as nonclassical monocytes or patrolling monocytes (PMo), are instrumental in mitigating VOCs in SCD by scavenging endothelial cell-attached (EC-attached) sickle RBCs and debris from hemolysis-damaged endothelium (12)(13)(14). In comparison with healthy donors (HD), patients with SCD exhibit reduced circulating PMo levels (12).…”