Patrolling Monocytes Scavenge Endothelial Adherent Sickle Red Blood Cells in Sickle Cell Disease

Sickle cell disease (SCD) is characterized by hemolytic anemia and increased entrapment of sickle red blood cells (RBCs) via attachment to the underlying activated vascular endothelium, resulting in vaso-occlusive crisis (VOC), marked by severe pain. The endothelial scavenging patrolling monocytes (PMos) expressing high levels of the heme oxygenase 1 (HO-1), a heme degrading enzyme, were recently shown to protect against vaso-occlusion in SCD, although their ability to scavenge endothelial-attached sickle RBCs was not tested. Here, we found that circulating PMos from SCD patients showed roughly 5% ± 0.5% engulfed GPA+ or Band3+ RBC specific material as compared to 0.7% ± 0.04% in healthy donor (HD) PMos or 0.85% ± 0.07% in SCD classical monocytes (CMos) as detected by flow as well as imagining flow cytometry, suggesting that PMos uptake RBCs in SCD. To further investigate this, RBCs purified from HDs (to mimic transfused cells) or SCD patients were labelled with CFSE, and co-cultured with purified monocytes without or with human microvascular endothelial cells (HMVEC). We found 11% ± 0.5% CFSE+ PMos in co-cultures with SCD RBCs in presence of HMVEC as compared to 2.7% ± 0.4% when cultured with HD RBCs, indicating that PMos engulf sickle RBCs, but not HD RBCs. Low levels of CFSE+ PMos (2-3%) were detected in cocultures with either sickle or control RBCs in the absence of HMVEC, implicating that PMos preferentially uptake endothelial cell (EC)...
Source: Blood - Category: Hematology Authors: Tags: 401. Basic Science and Clinical Practice in Blood Transfusion: Basic Science Source Type: research

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CONCLUSION: This case highlights the utility of LT as a viable treatment option for acute sickle cell intrahepatic cholestasis. PMID: 32231764 [PubMed]
Source: World Journal of Hepatology - Category: Gastroenterology Tags: World J Hepatol Source Type: research
We present a new method to obtain erythrocyte shape classification using peripheral blood smear sample images. The aim of the method is to segment the cells, to separate clusters and classify cells (circulars, elongated and others). We compared our method with state-of the-art. Results showed that our method with is superior for the diagnosis support of sickle cell anemia.
Source: Medical and Biological Engineering and Computing - Category: Biomedical Engineering Source Type: research
Demystifying Medicine Lecture Series Although the fundamental molecular pathophysiology of sickle cell anemia was elucidated in studies of this genetic disease starting more than 70 years ago, it is only in about the last two decades that this knowledge has led to specific therapies. Indeed in the last decade serious attention has turned to the possibility of a genetic cure of this condition. Have we finally cured sickle cell anemia? Not quite, but we may be on the cusp. Really. In a dozen clinical trials planned or underway, some at the NIH Clinical Center, researchers are applying gene therapy to cure this well-studied g...
Source: Videocast - All Events - Category: General Medicine Tags: Upcoming Events Source Type: video
CONCLUSION: This study bridges an important knowledge gap regarding symptoms, concerns and outcomes that matter to children living with life-limiting conditions and their families and informs service development and evaluation. PMID: 32081084 [PubMed - as supplied by publisher]
Source: Palliative Medicine - Category: Palliative Care Authors: Tags: Palliat Med Source Type: research
Title: Sickle Cell Disease (Anemia)Category: Diseases and ConditionsCreated: 12/31/1997 12:00:00 AMLast Editorial Review: 1/10/2020 12:00:00 AM
Source: MedicineNet Chronic Pain General - Category: Anesthesiology Source Type: news
Publication date: Available online 2 November 2019Source: Nitric OxideAuthor(s): Luis E.F. Almeida, Sayuri Kamimura, Celia M. de Souza Batista, Nicholas Spornick, Margaret Y. Nettleton, Elizabeth Walek, Meghann L. Smith, Julia Finkel, Deepika Darbari, Paul Wakim, Zenaide M.N. QuezadoAbstractThe hypothesis of decreased nitric oxide (NO) bioavailability in sickle cell disease (SCD) proposes that multiple factors leading to decreased NO production and increased consumption contributes to vaso-occlusion, pulmonary hypertension, and pain. The anion nitrite is central to NO physiology as it is an end product of NO metabolism and...
Source: Nitric Oxide - Category: Chemistry Source Type: research
Abstract Sickle cell disease (SCD) is among the most common genetic diseases in the United States, affecting approximately 100,000 people. In the United States, SCD is characterized by a shortened life expectancy of only about 50 years in severe subtypes, significant quality-of-life impairments, and increased healthcare utilization and spending. SCD is characterized by chronic hemolytic anemia, vaso-occlusion, and progressive vascular injury affecting multiple organ systems. The pathophysiology is directly related to polymerization of deoxygenated hemoglobin, leading to a cascade of pathologic events including ery...
Source: The American Journal of Managed Care - Category: Health Management Authors: Tags: Am J Manag Care Source Type: research
Inherited hemoglobin disorders, including beta-thalassemia (BT) and sickle-cell disease (SCD) are the most common monogenic diseases worldwide, with a global carrier frequency of over 5%. With migration they are becoming more common worldwide, making their management and care an increasing concern for health care systems.BT is characterized by an imbalance in the α/β-globin chain ratio, ineffective erythropoiesis, chronic hemolytic anemia, and compensatory haemopoietic expansion. Globally, there are over 25,000 births each year with transfusion-dependent thalassemia (TDT). The current available tr...
Source: Mediterranean Journal of Hematology and Infectious Diseases - Category: Hematology Source Type: research
While packed red blood cell (PRBC) transfusion therapy is a mainstay in the treatment of certain patients with sickle cell disease (SCD) and the standard of care for preoperative management, there are associated risks. Delayed hemolytic transfusion reaction (DHTR) is a risk of PRBC transfusion occurring 2 to 20 days from transfusion and typically presents with severe pain characteristic of vaso-occlusive crisis, fever, and hemolytic anemia. DHTRs are uncommon, occurring in only 4% to 11% of transfused patients with SCD, but may be catastrophic in nature with progression to multiorgan failure within hours. Here, we describe...
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Clinical and Laboratory Observations Source Type: research
Background: Thrombospondin-1 (TSP-1) and 25-hydroxyvitamin D (25-OHD) play significant roles in the pathogenesis of sickle cell anemia (SCA). TSP-1 enhances cellular adhesion/inflammation, hence contributing to vaso-occlusive crisis (VOC); vitamin D, in contrast, retards inflammation and may lower rate of pain episodes. We determined serum levels of TSP-1 and 25-OHD in Nigerian children with SCA and their matched hemoglobin AA controls; and assess the relationship between the 2 biomarkers. Methods: In total 90 children (32 SCA in steady state, 30 SCA in VOC, and 28 HbAA controls) were studied. Serum TSP-1 and 25-OHD l...
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Online Articles: Clinical and Laboratory Observations Source Type: research
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