Prominent role of platelets in the formation of circulating neutrophil-red cell heterocellular aggregates in sickle cell anemia

Dominical, Venina Marcela; Samsel, Leigh; Nichols, James S.; Costa, Fernando Ferreira; McCoy, J. Phillip; Conran, Nicola; Kato, Gregory J.

doi:10.3324/haematol.2014.108555

Cited by 36 publications

(37 citation statements)

References 15 publications

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“…In fact, the simultaneous inhibition of platelet P-selectin and neutrophil Mac-1 was potent enough to reduce the magnitude of platelet-neutrophil interactions in SCD human blood to that observed in control human blood. These findings are consistent with several flow cytometry-based studies that have confirmed the presence of circulating preformed neutrophil-platelet aggregates in the blood of steady-state SCD patients (12,13,33). Finally, we show that blocking P-selectin led to attenuation of pulmonary vaso-occlusions in SCD mice, which was primarily driven by the disintegration of large neutrophil-platelet aggregates into smaller aggregates that appear to rapidly transit through the arteriolar bottlenecks.…”

Section: Discussionsupporting

confidence: 79%

“…Finally, global inhibition of P-selectin and/or Mac-1 could affect host defense, due to the inability of neutrophils to recruit to sites of inflammation. SCD patients experience leukocytosis even under a steady-state condition (11,12,43), and therefore, interference with neutrophil recruitment can cause an elevation in circulating neutrophils. With these potential risks in mind, the targeted delivery of P-selectin or Mac-1 blockers as payloads in liposomes or nanocarriers designed to recruit specifically to the site of vaso-occlusion may represent an alternative approach for targeting vaso-occlusive crisis and pulmonary vaso-occlusion.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, neutrophil-platelet aggregates were observed in TNF-α-treated cremaster venules of SCD mice, requiring neutrophil Mac-1 binding to glycoprotein Ibα (GPIbα) on platelets (10). Interestingly, elevated platelet and leukocyte counts are identified risk factors for acute vaso-occlusive painful crisis (11), and circulating neutrophil-platelet aggregates are significantly elevated in the blood of steady-state SCD patients (12,13). Recent studies also suggest that neutrophil-platelet aggregates contribute to pulmonary inflammation in WT mice in the setting of acute lung injury (9,14).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Lung vaso-occlusion in sickle cell disease mediated by arteriolar neutrophil-platelet microemboli

Bennewitz¹,

Jimenez²,

Vats³

et al. 2017

JCI Insight

110

168

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Lung vaso-occlusion in sickle cell disease mediated by arteriolar neutrophil-platelet microemboli

Bennewitz¹,

Jimenez²,

Vats³

et al. 2017

JCI Insight

110

168

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“…One of the major complications of SCD arises from vaso-occlusion of rigid and distorted erythrocytes in small capillaries, which can potentially lead to death. However, elevated levels of leukocytes in the blood of SCD patients can also relate to disease severity and lead to an increased occurrence of vaso-occlusive events (11), as can leukocyte-RBC aggregation (11, 12). These circulating aggregates of cells have not been well documented in humans, partially due to the lack of acceptable methodology to explore this question.…”

Section: Sickle Cell Diseasementioning

confidence: 99%

“…Dominical and colleagues (11), in collaboration with our laboratory, expanded upon the ability of IFC to identify leukocyte:RBC aggregates and examined neutrophil:RBC aggregates in patient samples and the role of platelets in the formation of those aggregates. The granulocytic fraction obtained by Ficoll sedimentation of peripheral blood from healthy subjects and SCD patients was labeled with antibodies for CD66b (neutrophils), CD71 (reticulocytes), and CD235a (RBC).…”

Section: Sickle Cell Diseasementioning

confidence: 99%

Imaging flow cytometry for the study of erythroid cell biology and pathology

Samsel

McCoy

2015

Journal of Immunological Methods

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Erythroid cell maturation and diseases affecting erythrocytes are frequently accompanied by morphologic and immunophenotypic changes to these cells. In the past, these changes have been assessed primarily through the use of manual microscopy, which substantially limits the statistical rigor, throughput, and objectivity of these studies. Imaging flow cytometry provides a technology to examine both the morphology of cells as well as to quantify the staining intensity and signal distribution of numerous fluorescent markers on a cell-by-cell basis with high throughput in a statistically robust manner, and thus is ideally suited to studying erythroid cell biology. To date imaging flow cytometry has been used to study erythrocytes in three areas: 1) erythroid cell maturation, 2) sickle cell disease, and 3) infectious diseases such as malaria. In the maturation studies, imaging flow cytometry can closely recapitulate known stages of maturation and has led to the identification of a new population of erythroid cell precursors. In sickle cell disease, imaging flow cytometry provides a robust method to quantify sickled erythrocytes and to identify cellular aggregates linked to morbidities, and in malaria, imaging flow cytometry has been used to screen for new chemotherapeutic agents. These studies have demonstrated the value of imaging flow cytometry for investigations of erythrocyte biology and pathology.

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Neutrophils in sickle cell disease: Exploring their potential role as a therapeutic target

de Ligt,

Gaartman,

Biemond

et al. 2024

American J Hematol

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Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by chronic hemolytic anemia and recurrent microvascular occlusions, resulting in acute painful events and progressive organ damage. Although primarily a red blood cell disorder, the pathophysiology of SCD is increasingly characterized as a complex interplay between several different cell types and cellular processes. Evidence is accumulating that neutrophils are phenotypically different in SCD and have a significant contribution in the pathophysiology of the disease. In this review, we summarize the currently available evidence on the role of neutrophils in SCD pathophysiology, demonstrating that neutrophils in SCD have an activated phenotype and play an important role in vaso‐occlusion and inflammation in SCD. Activation of neutrophils in SCD is primarily driven by hemolysis and ischemia–reperfusion injury. The ameliorating effects of treatments, for example, hydroxyurea, might be partly mediated by decreasing neutrophil counts and reversing the pro‐inflammatory properties. Whether the novel anti‐sickling therapies, reducing hemolysis, have an anti‐inflammatory effect on neutrophils, remains to be elucidated.

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Prominent role of platelets in the formation of circulating neutrophil-red cell heterocellular aggregates in sickle cell anemia

Cited by 36 publications

References 15 publications

Lung vaso-occlusion in sickle cell disease mediated by arteriolar neutrophil-platelet microemboli

Lung vaso-occlusion in sickle cell disease mediated by arteriolar neutrophil-platelet microemboli

Imaging flow cytometry for the study of erythroid cell biology and pathology

Neutrophils in sickle cell disease: Exploring their potential role as a therapeutic target

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