Nucleosomes and neutrophil activation in sickle cell disease painful crisis

Schimmel, Marein; Nur, Erfan; Biemond, Bart J.; Mierlo, Gerard J. van; Solati, Shabnam; Brandjes, Dees P. M.; Otten, Hans-Martin; Schnog, John‐John B.; Zeerleder, Sacha

doi:10.3324/haematol.2013.088021

Cited by 69 publications

(58 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our findings, supported by a recent report of circulating nucleosomes in SCD patients admitted for VOC or ACS, 47 highlight a crucial role for heme in inducing NET formation in neutrophils after proinflammatory cytokine priming. The association of short alleles of the heme oxygenase-1 promoter (associated with higher enzyme activity) with lower rates of hospitalization for ACS 48 also supports our findings that NETs are generated in the pulmonary vasculature in SCD.…”

Section: Discussionsupporting

confidence: 79%

Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease

Chen

Zhang

Fuchs

et al. 2014

Blood

290

295

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 79%

Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease

Chen

Zhang

Fuchs

et al. 2014

Blood

290

295

View full text Add to dashboard Cite

show abstract

“…Our findings of elevated inflammatory biomarkers during sickle cell pain crisis are consistent with previous studies showing elevated neutrophil count and CRP in steady state with further elevation during pain crisis, though we did not observe an elevated neutrophil count in steady state compared with healthy individuals as previously reported. 13,14 The observational nature of this study does not allow us to causally link inflammation with increased oxygen consumption; however, these data emphasize the relevance of inflammation to the pathophysiology of sickle cell disease, especially during pain crisis. …”

mentioning

confidence: 93%

Microvascular oxygen consumption during sickle cell pain crisis

Rowley

Ikeda

Seidel

et al. 2014

Blood

View full text Add to dashboard Cite

• Patients with sickle cell disease have greater microvascular oxygen consumption rates than healthy individuals.• During sickle cell pain crisis, microvascular oxygen consumption increases further.Sickle cell disease is an inherited blood disorder characterized by chronic hemolytic anemia and episodic vaso-occlusive pain crises. Vaso-occlusion occurs when deoxygenated hemoglobin S polymerizes and erythrocytes sickle and adhere in the microvasculature, a process dependent on the concentration of hemoglobin S and the rate of deoxygenation, among other factors. We measured oxygen consumption in the thenar eminence during brachial artery occlusion in sickle cell patients and healthy individuals. IntroductionSickle cell disease is a blood disorder caused by homozygous or compound-heterozygous inheritance of abnormal hemoglobin-b chains that form hemoglobin S. Patients with sickle cell disease endure pain crises that may last days and occur multiple times each year.1,2 The etiology of painful crises is unknown but may involve blockage of vessels by sickled and adherent blood cells, 3 followed by ischemia reperfusion injury 4 and local inflammatory responses. Inflammation, in addition to increasing pain, can increase oxygen consumption 6,7 and might have adverse effects on hemoglobin oxygenation and sickling when oxygen delivery is limiting. We hypothesized that sickle cell patients would have increased rates of oxygen consumption during acute pain crisis. We measured microvascular oxygen consumption and systemic biomarkers of inflammation in healthy African American volunteers, in patients with sickle cell disease in clinical steady state, and in patients both during pain crisis and after recovery. Study design PatientsThe Institutional Review Board of the National Heart, Lung and Blood Institute approved clinical protocol 12-H-0101 specifically for this study. All participants provided written informed consent in accordance with the Declaration of Helsinki. See http://www.clinicaltrials.gov/ct2/show/ NCT01568710 and supplemental Table 1 (available on the Blood Web site) for enrollment criteria. Pain crisis was defined as acute pain occurring in a typical distribution requiring hospital admission and parenteral analgesia. Acute crisis studies were performed within 36 hours of admission, after patients had received intravenous fluids and pain medications. Follow-up studies were performed more than 3 weeks after resolution of acute pain symptoms. Near-infrared spectroscopy and oxygen consumption calculationNear-infrared spectroscopy has been validated against magnetic resonance spectroscopy as a measure of local oxygen consumption in muscle. 8 We used the Inspectra 650 (Hutchinson Technology, Hutchinson, MN) to record tissue hemoglobin oxygen saturation 9 (StO 2 ) and tissue hemoglobin index 10 (THI; a measure of hemoglobin signal strength) every 2 seconds during a 5-minute brachial artery occlusion. Oxygen consumption (VO 2 ) was calculated as the sum of each change in StO 2 over each 2-second interval, weighted by t...

show abstract

“…Neutrophils in particular have generated much interest in perpetuating the overall vascular pathology of SCD [101] and positively correlate with morbidity and mortality associated with the disease [102,103]. SCD neutrophils are hyper-adhesive to the vascular endothelium as well as to other cell types with excessive binding interactions in SCD producing an abnormal and highly-activated cellular environment.…”

Section: Cellular Cross-talk and Role Of Neutrophils In Scdmentioning

confidence: 99%

“…Upon activation, neutrophils release their extracellular traps (NETs). These chromatin structures form tangles of extracellular fibers that bind with sickled RBCs and platelets, forming multicellular complexes and provoking VOC [90,103]. We were the first to show neutrophils are responsible for an accelerated thrombus formation within the cerebral microvessels of mice with SCD [50].…”

Section: Cellular Cross-talk and Role Of Neutrophils In Scdmentioning

confidence: 99%

Sickle cell disease: a malady beyond a hemoglobin defect in cerebrovascular disease

Ansari

Moufarrej

Pawliński

et al. 2017

Expert Review of Hematology

View full text Add to dashboard Cite

Introduction Sickle cell disease (SCD) is a devastating monogenic disorder that presents as a multisystem illness and affects approximately 100,000 individuals in the United States alone. SCD management largely focuses on primary prevention, symptomatic treatment and targeting of hemoglobin polymerization and red blood cell sickling. Areas covered This review will discuss the progress of SCD over the last few decades, highlighting some of the clinical (mainly cerebrovascular) and psychosocial challenges of SCD in the United States. In addition, focus will also be made on the evolving science and management of this inherited disease. Expert Commentary Until recently hydroxyurea (HU) has been the only FDA approved therapy for SCD. However, advancing understanding of SCD pathophysiology has led to multiple clinical trials targeting SCD related thrombo-inflammation, abnormal endothelial biology, increased oxidant stress and sickle cell mutation. Yet, despite advancing understanding, available therapies are limited. SCD also imposes great psychosocial challenges for the individual and the affected community, which has previously been under-recognized. This has created a pressing need for complementary adjuvant therapies with repurposed and novel drugs, in addition to the establishment of comprehensive clinics focusing on both the medical treatment and the psychosocial issues associated with SCD.

show abstract

Nucleosomes and neutrophil activation in sickle cell disease painful crisis

Cited by 69 publications

References 52 publications

Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease

Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease

Microvascular oxygen consumption during sickle cell pain crisis

Sickle cell disease: a malady beyond a hemoglobin defect in cerebrovascular disease

Contact Info

Product

Resources

About