scholarly journals A Potential Role of the CD47/SIRPalpha Axis in COVID-19 Pathogenesis

2021 ◽  
Vol 43 (3) ◽  
pp. 1212-1225
Author(s):  
Katie-May McLaughlin ◽  
Denisa Bojkova ◽  
Joshua D. Kandler ◽  
Marco Bechtel ◽  
Philipp Reus ◽  
...  
Keyword(s):  
Immune Escape ◽  
Severe Disease ◽  
Kidney Injury ◽  
Bronchial Epithelial ◽  
Age Related ◽  
Literature Searches ◽  
Life Threatening ◽  
Infected Cells ◽  
Air Liquid Interface

The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Most SARS-CoV-2 infections are mild or even asymptomatic. However, a small fraction of infected individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. However, the factors predisposing individuals to severe disease remain poorly understood. Here, we show that levels of CD47, which is known to mediate immune escape in cancer and virus-infected cells, are elevated in SARS-CoV-2-infected Caco-2 cells, Calu-3 cells, and air−liquid interface cultures of primary human bronchial epithelial cells. Moreover, SARS-CoV-2 infection increases SIRPalpha levels, the binding partner of CD47, on primary human monocytes. Systematic literature searches further indicated that known risk factors such as older age and diabetes are associated with increased CD47 levels. High CD47 levels contribute to vascular disease, vasoconstriction, and hypertension, conditions that may predispose SARS-CoV-2-infected individuals to COVID-19-related complications such as pulmonary hypertension, lung fibrosis, myocardial injury, stroke, and acute kidney injury. Hence, age-related and virus-induced CD47 expression is a candidate mechanism potentially contributing to severe COVID-19, as well as a therapeutic target, which may be addressed by antibodies and small molecules. Further research will be needed to investigate the potential involvement of CD47 and SIRPalpha in COVID-19 pathology. Our data should encourage other research groups to consider the potential relevance of the CD47/ SIRPalpha axis in their COVID-19 research.

scholarly journals CD47 as a potential biomarker for the early diagnosis of severe COVID-19

2021 ◽  
Author(s):  
Katie-May McLaughlin ◽  
Denisa Bojkova ◽  
Marco Bechtel ◽  
Joshua D. Kandler ◽  
Philipp Reus ◽  
...  
Keyword(s):  
Early Identification ◽  
Myocardial Injury ◽  
Immune Escape ◽  
Kidney Injury ◽  
Model Systems ◽  
Literature Searches ◽  
Potential Biomarker ◽  
Risk Patients ◽  
Life Threatening ◽  
Infected Cells

AbstractThe coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Most SARS-CoV-2 infections are mild or even asymptomatic. However, a small fraction of infected individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. Antiviral interventions are only effective prior to the onset of hyperinflammation. Hence, biomarkers are needed for the early identification and treatment of high-risk patients. Here, we show in a range of model systems and data from post mortem samples that SARS-CoV-2 infection results in increased levels of CD47, which is known to mediate immune escape in cancer and virus-infected cells. Systematic literature searches also indicated that known risk factors such as older age and diabetes are associated with increased CD47 levels. High CD47 levels contribute to vascular disease, vasoconstriction, and hypertension, conditions which may predispose SARS-CoV-2-infected individuals to COVID-19-related complications such as pulmonary hypertension, lung fibrosis, myocardial injury, stroke, and acute kidney injury. Hence, CD47 is a candidate biomarker for severe COVID-19. Further research will have to show whether CD47 is a reliable diagnostic marker for the early identification of COVID-19 patients requiring antiviral therapy.

scholarly journals The Indirect Implication of SARS-CoV-2 Resulting in Kayexalate Toxicity in a Patient with Acute Kidney Injury

2021 ◽  
Vol 5 (1) ◽  
pp. 6-13
Author(s):  
Charles E. Middleton IV ◽  
William Daley ◽  
Neha Varshney
Keyword(s):  
Acute Kidney Injury ◽  
Virus Disease ◽  
Severe Disease ◽  
Kidney Injury ◽  
Multiple Organ ◽  
Subsequent Treatment ◽  
Gastrointestinal Complications ◽  
Treatment Regimens ◽  
Organ Systems ◽  
Life Threatening

The clinical features of corona virus disease 2019 (COVID-19) are variable, but the majority of patients experience mild flu-like symptoms. The cases of severe disease include complications such as progressive pneumonia, acute kidney injury, multi-organ failure, and even death. This paper explores the association between COVID-19 and its effect on multiple organ systems and how the subsequent treatment of this disease can itself lead to morbidity and mortality. We present a case which emphasizes the life threatening gastrointestinal complications associated with treatment of acute kidney injury (AKI) in a patient with COVID-19. We conclude that the patients whose treatment regimens utilize medical resins should be closely monitored for gastrointestinal complications so as to mitigate the known adverse effects associated with these drugs, such as colonic mucosal ulceration, perforation, or even death.

scholarly journals Role of BamHI-A Rightward Frame 1 in Epstein–Barr Virus-Associated Epithelial Malignancies

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 461
Author(s):  
Rancés Blanco ◽  
Francisco Aguayo
Keyword(s):  
Epstein Barr Virus ◽  
Immune Escape ◽  
Tumor Formation ◽  
Host Proteins ◽  
Barr Virus ◽  
Functional Aspects ◽  
Infected Cells ◽  
Epstein Barr ◽  
Apoptotic Effects

Epstein–Barr virus (EBV) infection is associated with a subset of both lymphoid and epithelial malignancies. During the EBV latency program, some viral products involved in the malignant transformation of infected cells are expressed. Among them, the BamHI-A rightward frame 1 (BARF1) is consistently detected in nasopharyngeal carcinomas (NPC) and EBV-associated gastric carcinomas (EBVaGCs) but is practically undetectable in B-cells and lymphomas. Although BARF1 is an early lytic gene, it is expressed during epithelial EBV latency, mainly as a secreted protein (sBARF1). The capacity of sBARF1 to disrupt both innate and adaptive host antiviral immune responses contributes to the immune escape of infected cells. Additionally, BARF1 increases cell proliferation, shows anti-apoptotic effects, and promotes an increased hTERT activity and tumor formation in nude mice cooperating with other host proteins such as c-Myc and H-ras. These facts allow for the consideration of BARF1 as a key protein for promoting EBV-associated epithelial tumors. In this review, we focus on structural and functional aspects of BARF1, such as mechanisms involved in epithelial carcinogenesis and its capacity to modulate the host immune response.

scholarly journals Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects?

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 968 ◽  
Author(s):  
Sunitha Kodidela ◽  
Kelli Gerth ◽  
Sanjana Haque ◽  
Yuqing Gong ◽  
Saifudeen Ismael ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Extracellular Vesicles ◽  
Treatment Strategies ◽  
Progressive Dementia ◽  
Hiv Patients ◽  
Age Related ◽  
Infected Cells ◽  
New Treatment

The longevity of people with HIV/AIDS has been prolonged with the use of antiretroviral therapy (ART). The age-related complications, especially cognitive deficits, rise as HIV patients live longer. Deposition of beta-amyloid (Aβ), a hallmark of Alzheimer’s disease (AD), has been observed in subjects with HIV-associated neurocognitive disorders (HAND). Various mechanisms such as neuroinflammation induced by HIV proteins (e.g., Tat, gp120, Nef), excitotoxicity, oxidative stress, and the use of ART contribute to the deposition of Aβ, leading to dementia. However, progressive dementia in older subjects with HIV might be due to HAND, AD, or both. Recently, extracellular vesicles (EVs)/exosomes, have gained recognition for their importance in understanding the pathology of both HAND and AD. EVs can serve as a possible link between HIV and AD, due to their ability to package and transport the toxic proteins implicated in both AD and HIV (Aβ/tau and gp120/tat, respectively). Given that Aß is also elevated in neuron-derived exosomes isolated from the plasma of HIV patients, it is reasonable to suggest that neuron-to-neuron exosomal transport of Aβ and tau also contributes to AD-like pathology in HIV-infected subjects. Therefore, exploring exosomal contents is likely to help distinguish HAND from AD. However, future prospective clinical studies need to be conducted to compare the exosomal contents in the plasma of HIV subjects with and without HAND as well as those with and without AD. This would help to find new markers and develop new treatment strategies to treat AD in HIV-positive subjects. This review presents comprehensive literatures on the mechanisms contributing to Aβ deposition in HIV-infected cells, the role of EVs in the propagation of Aβ in AD, the possible role of EVs in HIV-induced AD-like pathology, and finally, possible therapeutic targets or molecules to treat HIV subjects with AD.

scholarly journals Endotoxin-Induced Tryptophan Degradation along the Kynurenine Pathway: The Role of Indolamine 2,3-Dioxygenase and Aryl Hydrocarbon Receptor-Mediated Immunosuppressive Effects in Endotoxin Tolerance and Cancer and Its Implications for Immunoparalysis

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Elisa Wirthgen ◽  
Andreas Hoeflich
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Immune Escape ◽  
Endotoxin Tolerance ◽  
Kynurenine Pathway ◽  
Aryl Hydrocarbon ◽  
Tryptophan Degradation ◽  
Inflammatory Stimuli ◽  
Life Threatening ◽  
The Impact

The degradation of tryptophan (TRP) along the kynurenine pathway plays a crucial role as a neuro- and immunomodulatory mechanism in response to inflammatory stimuli, such as lipopolysaccharides (LPS). In endotoxemia or sepsis, an enhanced activation of the rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO) is associated with a higher mortality risk. It is assumed that IDO induced immunosuppressive effects provoke the development of a protracted compensatory hypoinflammatory phase up to a complete paralysis of the immune system, which is characterized by an endotoxin tolerance. However, the role of IDO activation in the development of life-threatening immunoparalysis is still poorly understood. Recent reports described the impact of inflammatory IDO activation and aryl hydrocarbon receptor- (AhR-) mediated pathways on the development of LPS tolerance and immune escape of cancer cells. These immunosuppressive mechanisms offer new insights for a better understanding of the development of cellular dysfunctions in immunoparalysis. This review provides a comprehensive update of significant biological functions of TRP metabolites along the kynurenine pathway and the complex regulation of LPS-induced IDO activation. In addition, the review focuses on the role of IDO-AhR-mediated immunosuppressive pathways in endotoxin tolerance and carcinogenesis revealing the significance of enhanced IDO activity for the establishment of life-threatening immunoparalysis in sepsis.

scholarly journals Role of Cigarette Smoke on Angiotensin-Converting Enzyme-2 Protein Membrane Expression in Bronchial Epithelial Cells Using an Air-Liquid Interface Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Massimo Caruso ◽  
Alfio Distefano ◽  
Rosalia Emma ◽  
Michelino Di Rosa ◽  
Giuseppe Carota ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Selective Reduction ◽  
Bronchial Epithelial Cells ◽  
Liquid Interface ◽  
Membrane Expression ◽  
Bronchial Epithelial ◽  
Prevalence Studies ◽  
Positive Direct ◽  
Air Liquid Interface

Prevalence studies of current smoking, among hospitalized COVID-19 patients, demonstrated an unexpectedly low prevalence among patients with COVID-19. The aim of the present study was to evaluate the effect of smoke from cigarettes on ACE-2 in bronchial epithelial cells. Normal bronchial epithelial cells (H292) were exposed to smoke by an air-liquid-interface (ALI) system and ACE-2 membrane protein expression was evaluated after 24 h from exposure. Our transcriptomics data analysis showed a significant selective reduction of membrane ACE-2 expression (about 25%) following smoking exposure. Interestingly, we observed a positive direct correlation between ACE-2 reduction and nicotine delivery. Furthermore, by stratifying GSE52237 as a function of ACE-2 gene expression levels, we highlighted 1,012 genes related to ACE-2 in smokers and 855 in non-smokers. Furthermore, we showed that 161 genes involved in the endocytosis process were highlighted using the online pathway tool KEGG. Finally, 11 genes were in common between the ACE-2 pathway in smokers and the genes regulated during endocytosis, while 12 genes with non-smokers. Interestingly, six in non-smokers and four genes in smokers were closely involved during the viral internalization process. Our data may offer a pharmaceutical role of nicotine as potential treatment option in COVID-19.

scholarly journals Critical Care COVID-19 Patient with a Picture of Thrombotic Thrombocytopenic Purpura

2020 ◽  
Author(s):  
Rehab AL-Ansari ◽  
Mohanad Bakkar ◽  
Leena Abdalla ◽  
Khaled Sewify
Keyword(s):  
Mechanical Ventilation ◽  
Critical Care ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Kidney Injury ◽  
Therapeutic Plasma Exchange ◽  
Thrombocytopenic Purpura ◽  
Threatening Condition ◽  
Life Threatening

Background: Thrombotic thrombocytopenic purpura (TTP) is an uncommon haematological disease which can occur at any age and may present with COVID-19. This case describes a COVID-19 complication associated with a presentation resembling TTP. Case description: A 51-year-old man who had received a kidney transplant and was on immunosuppressant medication, was admitted to a critical care unit with severe COVID-19 pneumonia/acute respiratory distress syndrome (ARDS) which required intubation, mechanical ventilation and inotropic support. The course was complicated by the classic pentad of thrombocytopenia, intravascular haemolysis, acute kidney injury, neurological symptoms and fever, which prompted the diagnosis of probable TTP. After five sessions of therapeutic plasma exchange, the patient’s general status improved, he was weaned off mechanical ventilation and his renal panel and haemolytic markers normalized. Conclusion: TTP is a life-threatening condition which requires urgent management with therapeutic plasma exchange. This case highlights some possible complications of COVID-19 generally and in immunocompromised patients specifically. The potential role of plasma exchange in COVID-19 patients without a positive diagnosis of TTP (the so-called ‘TTP resembling presentation’) is an area of further research.

scholarly journals Involvement of high mobility group box 1 in the pathogenesis of severe hemolytic uremic syndrome in a murine model

2019 ◽  
Vol 317 (6) ◽  
pp. F1420-F1429 ◽  
Author(s):  
Ryo Maeda ◽  
Yukihiko Kawasaki ◽  
Yohei Kume ◽  
Hayato Go ◽  
Kazuhide Suyama ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Murine Model ◽  
Severe Disease ◽  
High Mobility ◽  
Kidney Injury ◽  
Saline Group ◽  
High Mobility Group ◽  
Uremic Syndrome ◽  
Group D

Typical hemolytic uremic syndrome is caused by Shiga toxin (Stx2) and lipopolysaccharide (LPS) of Escherichia coli and leads to acute kidney injury. The role of innate immunity in this pathogenesis is unclear. We analyzed the role of high mobility group box 1 (HMGB1) at the onset of disease in a murine model. C57BL/6 mice were intraperitoneally administered saline ( group A), anti-HMGB1 monoclonal antibody ( group B), Stx2 and LPS to elicit severe disease ( group C), or Stx2, LPS, and anti-HMGB1 antibody ( group D). While all mice in group C died by day 5 of the experiment, all mice in group D survived. Anemia and thrombocytopenia were pronounced and plasma creatinine levels were significantly elevated in group C only at 72 h. While at 72 h after toxin administration the glomerulus tissue in group C showed pathology similar to that of humans, mesangial cell proliferation was seen in group D. Plasma HMGB1 levels in group C peaked 3 h after administration and were higher than those in other groups. Expression of the receptor of advanced glycation end products and NF-κB, involved in HMGB1 signaling, was significantly elevated in group C but not in group D. Administration of anti-HMGB1 antibody in a murine model of severe disease inhibited plasma HMGB1 and promoted amelioration of tissue damage. HMGB1 was found to be involved in the disease pathology; therefore, controlling HMGB1 activity might inhibit disease progression.

Abstract 494: P21 Plays a Protective Role Against Renal Ischemia Reperfusion Injury and is an Essential Factor for Ischemic Preconditioning

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Satoshi Nishioka ◽  
Daisuke Nakano ◽  
Kento Kitada ◽  
Hiroyuki Ohosaki ◽  
Tadashi Sofue ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Protective Role ◽  
Renal Ischemia ◽  
Histological Changes ◽  
Sham Surgery ◽  
Life Threatening

Background: We previously reported that various pathological conditions including high blood pressure increase p21 expression in the kidney; however, the functional importance of renal p21 up-regulation has not been clarified yet. In the present study, we evaluated the role of p21 in acute kidney injury, a life-threatening disease that can occur independently of the pathological background of patients (whether renal p21 is up-regulated or not). Methods and Results: The mice lacking functional p21 (p21-KO, n=9) and its wild-type control (WT, n=7) underwent a 45-min renal ischemia followed by a 24-h reperfusion (I/R). I/R significantly increased both mRNA expression and nuclear immunoreactivity of p21 in the kidney of WT compared with sham surgery (p21/β-actin, 1.28±0.23 vs. 0.57±0.15, respectively, P<0.05). I/R injury analyzed by blood urea nitrogen (BUN) and kidney histological changes were exacerbated in p21-KO mice (BUN: WT; 103.8±4.6 mg/dL, p21-KO; 127.7±5.2 mg/dL, P<0.05). The results suggest that p21 plays a protective role against I/R injury. Therefore, we next examined whether p21 is also associated with the protective effect of ischemic preconditioning (IPC), which is an established method of attenuating the I/R injury. IPC (4 sets of a 5-min ischemia and a 5-min reperfusion) clearly improved the I/R injury in WT (BUN: sham; 87.7±22.0 mg/dL, IPC; 39.0±2.3 mg/dL, n=3 and n=7, respectively, P<0.05), whereas there was no difference in the I/R injury in p21-KO mice (BUN: sham; 136.5±13.6 mg/dL, IPC; 127.9±6.9 mg/dL, n=5 and n=8, respectively). IPC increased the renal expression of p21 prior to I/R compared with sham surgery (p21/β-actin: 1.07±0.08 vs. 0.26±0.05 fold, respectively, P<0.05). Conclusion: Renal p21 plays a protective role against I/R injury and is necessary for the beneficial effect of renal IPC.

Acute kidney injury

2020 ◽  
pp. 135-156
Author(s):  
Cristina Osorio ◽  
Theofanis Fotis
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Function ◽  
Nursing Care ◽  
Early Identification ◽  
Kidney Injury ◽  
Anatomy And Physiology ◽  
Renal Replacement Therapies ◽  
Life Threatening ◽  
Kidney Anatomy

Assessing and supporting kidney function is an integral aspect of acute care. AKI (acute kidney injury) may cause sudden, life-threatening biochemical disturbances and hence the early identification, escalation to treatment and management of AKI is an important focus in the management of acutely ill patients. This chapter reviews kidney anatomy and physiology followed by the nursing care involved in assessing and managing abnormal kidney function. The focus is on relevance and applicability to clinical practice and understanding of kidney function as protective measures and early detection of anomalies greatly reduces the risk of acute kidney injury. Common renal pathologies are explored and the role of renal replacement therapies is discussed.

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