Erythroid precursors and progenitors suppress adaptive immunity and get invaded by SARS-CoV-2

Shahbaz, Shima; Xu, Lai; Osman, Mohammed; Sligl, Wendy; Shields, Justin; Joyce, Michael; Tyrrell, D. Lorne; Oyegbami, Olaide; Elahi, Shokrollah

doi:10.1016/j.stemcr.2021.04.001

Cited by 77 publications

(105 citation statements)

References 72 publications

(109 reference statements)

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“…In a previous study, 200 μM HOCl was found to react with and destroy the heme of hemoglobin in red blood cells [ 12 ]. This is consistent with recent work by Elahi et al, in which the harmful effect of COVID-19 on red blood cells is demonstrated [ 46 ].…”

Section: Hocl-associated Hemoprotein Heme Destructionsupporting

confidence: 94%

Melatonin interferes with COVID-19 at several distinct ROS-related steps

Camp

Bai

Gonullu

et al. 2021

Journal of Inorganic Biochemistry

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Recent studies have shown a correlation between COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the distinct, exaggerated immune response titled “cytokine storm”. This immune response leads to excessive production and accumulation of reactive oxygen species (ROS) that cause clinical signs characteristic of COVID-19 such as decreased oxygen saturation, alteration of hemoglobin properties, decreased nitric oxide (NO) bioavailability, vasoconstriction, elevated cytokines, cardiac and/or renal injury, enhanced D-dimer, leukocytosis, and an increased neutrophil to lymphocyte ratio. Particularly, neutrophil myeloperoxidase (MPO) is thought to be especially abundant and, as a result, contributes substantially to oxidative stress and the pathophysiology of COVID-19. Conversely, melatonin, a potent MPO inhibitor, has been noted for its anti-inflammatory, anti-oxidative, anti-apoptotic, and neuroprotective actions. Melatonin has been proposed as a safe therapeutic agent for COVID-19 recently, having been given with a US Food and Drug Administration emergency authorized cocktail, REGEN-COV2, for management of COVID-19 progression. This review distinctly highlights both how the destructive interactions of HOCl with tetrapyrrole rings may contribute to oxygen deficiency and hypoxia, vitamin B12 deficiency, NO deficiency, increased oxidative stress, and sleep disturbance, as well as how melatonin acts to prevent these events, thereby improving COVID-19 prognosis.

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Section: Hocl-associated Hemoprotein Heme Destructionsupporting

confidence: 94%

Melatonin interferes with COVID-19 at several distinct ROS-related steps

Camp

Bai

Gonullu

et al. 2021

Journal of Inorganic Biochemistry

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“…The virus can infect erythroid precursor cells. This, in turn, leads to a greater production of immature red blood cells, followed by their massive release into the bloodstream and a corresponding drop in hemoglobin levels [ 24 ].…”

Section: Factors Determining the Disruption Of Gas Exchange In Covid-19mentioning

confidence: 99%

The Role of Acidosis in the Pathogenesis of Severe Forms of COVID-19

Nechipurenko

Semyonov

Lavrinenko

et al. 2021

Biology

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COVID-19 has specific characteristics that distinguish this disease from many other infections. We suggest that the pathogenesis of severe forms of COVID-19 can be associated with acidosis. This review article discusses several mechanisms potentially linking the damaging effects of COVID-19 with acidosis and shows the existence of a vicious cycle between the development of hypoxia and acidosis in COVID-19 patients. At the early stages of the disease, inflammation, difficulty in gas exchange in the lungs and thrombosis collectively contribute to the onset of acidosis. In accordance with the Verigo-Bohr effect, a decrease in blood pH leads to a decrease in oxygen saturation, which contributes to the exacerbation of acidosis and results in a deterioration of the patient’s condition. A decrease in pH can also cause conformational changes in the S-protein of the virus and thus lead to a decrease in the affinity and avidity of protective antibodies. Hypoxia and acidosis lead to dysregulation of the immune system and multidirectional pro- and anti-inflammatory reactions, resulting in the development of a “cytokine storm”. In this review, we highlight the potential importance of supporting normal blood pH as an approach to COVID-19 therapy.

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“…Extensive studies revealed its neglected immunomodulatory properties under other different physiological and pathological conditions, too. CEC is heterogeneous, which could be induced by tumor, injury (8), pregnancy (9), systemic inflammation (10), HIV infection (11), and even COVID-19 (12,13). All phenotypes have immunomodulatory functions.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound-Targeted Microbubble Destruction Alleviates Immunosuppression Induced by CD71+ Erythroid Progenitor Cells and Promotes PDL-1 Blockade Immunotherapy in the Lewis Lung Cancer Model

Tan¹,

Yi²,

Zhang³

et al. 2021

Front. Oncol.

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The CD71+ erythroid progenitor cells (CECs) exhibit distinctive immunosuppressive properties and regulate antitumor immunity to enable tumor growth. We presented a novel and non-invasive approach to improving immunity by targeting the splenic CECs via sonoporation generated by ultrasound-targeted microbubble destruction (UTMD). The systematic immunity enhanced by the reduction of PDL-1-expressing CECs also benefits the PDL-1 blockade therapy. In the Lewis lung cancer (LLC) model, the study group was treated by UTMD for 10 min at the splenic area with or without anti-mouse PDL-1 intraperitoneal injection. The frequency of splenic CEC, lymphocyte, and cytokine production was analyzed by flow cytometry. Serum interleukin-2 (IL-2) was tested by ELISA. Tumor volume was evaluated by two-dimensional ultrasound. The UTMD treatment consisted of ultrasound sonication and Sonazoid™ microbubble injection through the caudal vein. The mechanic index (MI) of ultrasound was set between 0.98 and 1.03. The results showed a significant reduction of splenic CECs and increased frequency of CD8+ T cells treated by UTMD treatment in the late-stage tumor. Tumor growth could be inhibited by UTMD combined with PDL-1 blockade therapy. The frequencies of interferon-γ (IFN-γ) producing CD8+ and CD4+ T cells were significantly increased after being treated by the combination of UTMD and PDL-1 blockade, while the reactive oxygen species (ROS) production and the fraction of the TGF-β-producing CD11b+ cells were significantly decreased. These preliminary findings suggest that UTMD enhances immune response and facilitates PDL-1 blockade therapy by targeting immunosuppressive CECs in the spleen. Our study provides new aspects and possibilities for treating cancer-related infection and tumor control in oncology.

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Erythroid precursors and progenitors suppress adaptive immunity and get invaded by SARS-CoV-2

Cited by 77 publications

References 72 publications

Melatonin interferes with COVID-19 at several distinct ROS-related steps

Melatonin interferes with COVID-19 at several distinct ROS-related steps

The Role of Acidosis in the Pathogenesis of Severe Forms of COVID-19

Ultrasound-Targeted Microbubble Destruction Alleviates Immunosuppression Induced by CD71+ Erythroid Progenitor Cells and Promotes PDL-1 Blockade Immunotherapy in the Lewis Lung Cancer Model

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