A Potential Role of the CD47/SIRPalpha Axis in COVID-19 Pathogenesis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Virus Infection
2.3. Western Blot
2.4. qPCR
2.5. Data Acquisition and Analysis
2.6. Literature Review
3. Results
3.1. SARS-CoV-2 Infection Results in Enhanced CD47 Expression
3.2. Increased SIRPα Levels in SARS-CoV-2-Infected Monocytes
3.3. CD47 and COVID-19 Risk Factors
3.3.1. CD47 and Aging
3.3.2. CD47 and Diabetes
3.3.3. CD47 and Obesity
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Hokello, J.; Sharma, A.L.; Shukla, G.C.; Tyagi, M. A narrative review on the basic and clinical aspects of the novel SARS-CoV-2, the etiologic agent of COVID-19. Ann. Transl. Med. 2020, 8, 1686. [Google Scholar] [CrossRef] [PubMed]
- Chilamakuri, R.; Agarwal, S. COVID-19: Characteristics and Therapeutics. Cells 2021, 10, 206. [Google Scholar] [CrossRef] [PubMed]
- Dong, E.; Du, H.; Gardner, L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect. Dis. 2020, 20, 533–534. [Google Scholar] [CrossRef]
- Shah, H.; Khan, M.S.H.; Dhurandhar, N.V.; Hegde, V. The triumvirate: Why hypertension, obesity, and diabetes are risk factors for adverse effects in patients with COVID-19. Acta Diabetol. 2021, 58, 831–843. [Google Scholar] [CrossRef] [PubMed]
- Andreano, E.; Piccini, G.; Licastro, D.; Casalino, L.; Johnson, N.V.; Paciello, I.; Monego, S.D.; Pantano, E.; Manganaro, N.; Manenti, A.; et al. SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 convalescent plasma. bioRxiv 2020. [Google Scholar] [CrossRef]
- Kemp, S.A.; Collier, D.A.; Datir, R.; Ferreira, I.; Gayed, S.; Jahun, A.; Hosmillo, M.; Rees-Spear, C.; Mlcochova, P.; Lumb, I.U.; et al. Neutralising antibodies in Spike mediated SARS-CoV-2 adaptation. medRxiv 2020. [Google Scholar] [CrossRef]
- Liu, Z.; VanBlargan, L.A.; Rothlauf, P.W.; Bloyet, L.M.; Chen, R.E.; Stumpf, S.; Zhao, H.; Errico, J.M.; Theel, E.S.; Ellebedy, A.H.; et al. Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization. bioRxiv 2020. [Google Scholar] [CrossRef]
- Weisblum, Y.; Schmidt, F.; Zhang, F.; DaSilva, J.; Poston, D.; Lorenzi, J.C.; Muecksch, F.; Rutkowska, M.; Hoffmann, H.H.; Michailidis, E.; et al. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. Elife 2020, 9, e61312. [Google Scholar] [CrossRef]
- Sabino, E.C.; Buss, L.F.; Carvalho, M.P.S.; Prete, C.A., Jr.; Crispim, M.A.E.; Fraiji, N.A.; Pereira, R.H.M.; Parag, K.V.; da Silva Peixoto, P.; Kraemer, M.U.G.; et al. Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence. Lancet 2021, 397, 452–455. [Google Scholar] [CrossRef]
- Wibmer, C.K.; Ayres, F.; Hermanus, T.; Madzivhandila, M.; Kgagudi, P.; Lambson, B.E.; Vermeulen, M.; van den Berg, K.; Rossouw, T.; Boswell, M.; et al. SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. bioRxiv 2021. [Google Scholar] [CrossRef]
- Rebold, N.; Holger, D.; Alosaimy, S.; Morrisette, T.; Rybak, M. COVID-19: Before the Fall, An Evidence-Based Narrative Review of Treatment Options. Infect. Dis. Ther. 2021, 10, 93–113. [Google Scholar] [CrossRef] [PubMed]
- Pum, A.; Ennemoser, M.; Adage, T.; Kungl, A.J. Cytokines and Chemokines in SARS-CoV-2 Infections-Therapeutic Strategies Targeting Cytokine Storm. Biomolecules 2021, 11, 91. [Google Scholar] [CrossRef] [PubMed]
- RECOVERY Collaborative Group; Horby, P.; Lim, W.S.; Emberson, J.R.; Mafham, M.; Bell, J.L.; Linsell, L.; Staplin, N.; Brightling, C.; Ustianowski, A.; et al. Dexamethasone in Hospitalized Patients with Covid-19—Preliminary Report. N. Engl. J. Med. 2021, 384, 693–704. [Google Scholar] [CrossRef] [PubMed]
- WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group; Sterne, J.A.C.; Murthy, S.; Diaz, J.V.; Slutsky, A.S.; Villar, J.; Angus, D.C.; Annane, D.; Azevedo, L.C.P.; Berwanger, O.; et al. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA 2020, 324, 1330–1341. [Google Scholar] [PubMed]
- Hadid, T.; Kafri, Z.; Al-Katib, A. Coagulation and anticoagulation in COVID-19. Blood Rev. 2020, 100761. [Google Scholar] [CrossRef] [PubMed]
- Beigel, J.H.; Tomashek, K.M.; Dodd, L.E.; Mehta, A.K.; Zingman, B.S.; Kalil, A.C.; Hohmann, E.; Chu, H.Y.; Luetkemeyer, A.; Kline, S.; et al. Remdesivir for the Treatment of Covid-19—Final Report. N. Engl. J. Med. 2020, 383, 1813–1826. [Google Scholar] [CrossRef]
- Kalil, A.C.; Patterson, T.F.; Mehta, A.K.; Tomashek, K.M.; Wolfe, C.R.; Ghazaryan, V.; Marconi, V.C.; Ruiz-Palacios, G.M.; Hsieh, L.; Kline, S.; et al. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. N. Engl. J. Med. 2021, 384, 795–807. [Google Scholar] [CrossRef]
- Tuccori, M.; Ferraro, S.; Convertino, I.; Cappello, E.; Valdiserra, G.; Blandizzi, C.; Maggi, F.; Focosi, D. Anti-SARS-CoV-2 neutralizing monoclonal antibodies: Clinical pipeline. MAbs 2020, 12, 1854149. [Google Scholar] [CrossRef]
- Devarasetti, P.K.; Rajasekhar, L.; Baisya, R.; Sreejitha, K.S.; Vardhan, Y.K. A review of COVID-19 convalescent plasma use in COVID-19 with focus on proof of efficacy. Immunol. Res. 2021, 69, 18–25. [Google Scholar] [CrossRef]
- Weinreich, D.M.; Sivapalasingam, S.; Norton, T.; Ali, S.; Gao, H.; Bhore, R.; Musser, B.J.; Soo, Y.; Rofail, D.; Im, J.; et al. REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N. Engl. J. Med. 2021, 384, 238–251. [Google Scholar] [CrossRef]
- Salzberger, B.; Buder, F.; Lampl, B.; Ehrenstein, B.; Hitzenbichler, F.; Holzmann, T.; Schmidt, B.; Hanses, F. Epidemiology of SARS-CoV-2. Infection 2020, 49, 233–239. [Google Scholar] [CrossRef]
- Cham, L.B.; Adomati, T.; Li, F.; Ali, M.; Lang, K.S. CD47 as a Potential Target to Therapy for Infectious Diseases. Antibodies 2020, 9, 44. [Google Scholar] [CrossRef]
- Kaur, S.; Cicalese, K.V.; Bannerjee, R.; Roberts, D.D. Preclinical and Clinical Development of Therapeutic Antibodies Targeting Functions of CD47 in the Tumor Microenvironment. Antib. Ther. 2020, 3, 179–192. [Google Scholar] [CrossRef] [PubMed]
- Tal, M.C.; Torrez Dulgeroff, L.B.; Myers, L.; Cham, L.B.; Mayer-Barber, K.D.; Bohrer, A.C.; Castro, E.; Yiu, Y.Y.; Lopez Angel, C.; Pham, E.; et al. Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition. mBio 2020, 11, e01293-20. [Google Scholar] [CrossRef] [PubMed]
- Hoehl, S.; Berger, A.; Kortenbusch, M.; Cinatl, J.; Bojkova, D.; Rabenau, H.; Behrens, P.; Böddinghaus, B.; Götsch, U.; Naujoks, F.; et al. Evidence of SARS-CoV-2 Infection in Returning Travelers from Wuhan, China. N. Engl. J. Med. 2020, 382, 1278–1280. [Google Scholar] [CrossRef] [PubMed]
- Toptan, T.; Hoehl, S.; Westhaus, S.; Bojkova, D.; Berger, A.; Rotter, B.; Hoffmeier, K.; Cinatl, J., Jr.; Ciesek, S.; Widera, M. Optimized qRT-PCR Approach for the Detection of Intra- and Extra-Cellular SARS-CoV-2 RNAs. Int. J. Mol. Sci. 2020, 21, 4396. [Google Scholar] [CrossRef]
- Cinatl, J.; Morgenstern, B.; Bauer, G.; Chandra, P.; Rabenau, H.; Doerr, H.W. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet 2003, 361, 2045–62046. [Google Scholar] [CrossRef] [Green Version]
- Cinatl, J., Jr.; Michaelis, M.; Morgenstern, B.; Doerr, H.W. High-dose hydrocortisone reduces expression of the pro-inflammatory chemokines CXCL8 and CXCL10 in SARS coronavirus-infected intestinal cells. Int. J. Mol. Med. 2005, 15, 323–327. [Google Scholar] [CrossRef]
- Bojkova, D.; Klann, K.; Koch, B.; Widera, M.; Krause, D.; Ciesek, S.; Cinatl, J.; Münch, C. Proteomics of SARS-CoV-2-infected host cells reveals therapy targets. Nature 2020, 583, 469–472. [Google Scholar] [CrossRef] [PubMed]
- Perez-Riverol, Y.; Csordas, A.; Bai, J.; Bernal-Llinares, M.; Hewapathirana, S.; Kundu, D.J.; Inuganti, A.; Griss, J.; Mayer, G.; Eisenacher, M.; et al. The PRIDE database and related tools and resources in 2019: Improving support for quantification data. Nucleic Acids Res. 2019, 47, D442–D450. [Google Scholar] [CrossRef]
- Blanco-Melo, D.; Nilsson-Payant, B.E.; Liu, W.C.; Uhl, S.; Hoagland, D.; Møller, R.; Jordan, T.X.; Oishi, K.; Panis, M.; Sachs, D.; et al. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell 2020, 181, 1036–1045.e9. [Google Scholar] [CrossRef] [PubMed]
- Bojkova, D.; Bechtel, M.; McLaughlin, K.M.; McGreig, J.E.; Klann, K.; Bellinghausen, C.; Rohde, G.; Jonigk, D.; Braubach, P.; Ciesek, S.; et al. Aprotinin Inhibits SARS-CoV-2 Replication. Cells 2020, 9, 2377. [Google Scholar] [CrossRef] [PubMed]
- Bou Ghanem, E.N.; Clark, S.; Du, X.; Wu, D.; Camilli, A.; Leong, J.M.; Meydani, S.N. The α-tocopherol form of vitamin E reverses age-associated susceptibility to streptococcus pneumoniae lung infection by modulating pulmonary neutrophil recruitment. J. Immunol. 2015, 194, 1090–1099. [Google Scholar] [CrossRef] [Green Version]
- Isenberg, J.S.; Frazier, W.A.; Roberts, D.D. Thrombospondin-1: A physiological regulator of nitric oxide signaling. Cell. Mol. Life Sci. 2008, 65, 728–742. [Google Scholar] [CrossRef] [Green Version]
- Miller, T.W.; Isenberg, J.S.; Roberts, D.D. Thrombospondin-1 is an inhibitor of pharmacological activation of soluble guanylate cyclase. Br. J. Pharmacol. 2010, 159, 1542–1547. [Google Scholar] [CrossRef] [Green Version]
- Touyz, R.M.; Alves-Lopes, R.; Rios, F.J.; Camargo, L.L.; Anagnostopoulou, A.; Arner, A.; Montezano, A.C. Vascular smooth muscle contraction in hypertension. Cardiovasc. Res. 2018, 114, 529–539. [Google Scholar] [CrossRef] [Green Version]
- Isenberg, J.S.; Hyodo, F.; Pappan, L.K.; Abu-Asab, M.; Tsokos, M.; Krishna, M.C.; Frazier, W.A.; Roberts, D.D. Blocking thrombospondin-1/CD47 signaling alleviates deleterious effects of aging on tissue responses to ischemia. Arterioscler. Thromb. Vasc. Biol. 2007, 27, 2582–2588. [Google Scholar] [CrossRef] [Green Version]
- Isenberg, J.S.; Qin, Y.; Maxhimer, J.B.; Sipes, J.M.; Despres, D.; Schnermann, J.; Frazier, W.A.; Roberts, D.D. Thrombospondin-1 and CD47 regulate blood pressure and cardiac responses to vasoactive stress. Matrix Biol. 2009, 28, 110–119. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Frazier, E.P.; Isenberg, J.S.; Shiva, S.; Zhao, L.; Schlesinger, P.; Dimitry, J.; Abu-Asab, M.S.; Tsokos, M.; Roberts, D.D.; Frazier, W.A. Age-dependent regulation of skeletal muscle mitochondria by the thrombospondin-1 receptor CD47. Matrix Biol. 2011, 30, 154–161. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bauer, P.M.; Bauer, E.M.; Rogers, N.M.; Yao, M.; Feijoo-Cuaresma, M.; Pilewski, J.M.; Champion, H.C.; Zuckerbraun, B.S.; Calzada, M.J.; Isenberg, J.S. Activated CD47 promotes pulmonary arterial hypertension through targeting caveolin-1. Cardiovasc. Res. 2012, 93, 682–693. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rogers, N.M.; Sharifi-Sanjani, M.; Yao, M.; Ghimire, K.; Bienes-Martinez, R.; Mutchler, S.M.; Knupp, H.E.; Baust, J.; Novelli, E.M.; Ross, M.; et al. TSP1-CD47 signaling is upregulated in clinical pulmonary hypertension and contributes to pulmonary arterial vasculopathy and dysfunction. Cardiovasc. Res. 2017, 113, 15–29. [Google Scholar] [CrossRef] [PubMed]
- Rogers, N.M.; Roberts, D.D.; Isenberg, J.S. Age-associated induction of cell membrane CD47 limits basal and temperature-induced changes in cutaneous blood flow. Ann. Surg. 2013, 258, 184–191. [Google Scholar] [CrossRef] [Green Version]
- Nevitt, C.; McKenzie, G.; Christian, K.; Austin, J.; Hencke, S.; Hoying, J.; LeBlanc, A. Physiological levels of thrombospondin-1 decrease NO-dependent vasodilation in coronary microvessels from aged rats. Am. J. Physiol. Heart Circ. Physiol. 2016, 310, H1842–H1850. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gao, Q.; Chen, K.; Gao, L.; Zheng, Y.; Yang, Y.G. Thrombospondin-1 signaling through CD47 inhibits cell cycle progression and induces senescence in endothelial cells. Cell Death Dis. 2016, 7, e2368. [Google Scholar] [CrossRef] [PubMed]
- Meijles, D.N.; Sahoo, S.; Al Ghouleh, I.; Amaral, J.H.; Bienes-Martinez, R.; Knupp, H.E.; Attaran, S.; Sembrat, J.C.; Nouraie, S.M.; Rojas, M.M.; et al. The matricellular protein TSP1 promotes human and mouse endothelial cell senescence through CD47 and Nox1. Sci. Signal. 2017, 10, eaaj1784. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ghimire, K.; Li, Y.; Chiba, T.; Julovi, S.M.; Li, J.; Ross, M.A.; Straub, A.C.; O’Connell, P.J.; Rüegg, C.; Pagano, P.J.; et al. CD47 Promotes Age-Associated Deterioration in Angiogenesis, Blood Flow and Glucose Homeostasis. Cells 2020, 9, 1695. [Google Scholar] [CrossRef] [PubMed]
- Rogers, N.M.; Yao, M.; Sembrat, J.; George, M.P.; Knupp, H.; Ross, M.; Sharifi-Sanjani, M.; Milosevic, J.; St Croix, C.; Rajkumar, R.; et al. Cellular, pharmacological, and biophysical evaluation of explanted lungs from a patient with sickle cell disease and severe pulmonary arterial hypertension. Pulm. Circ. 2013, 3, 936–951. [Google Scholar] [CrossRef] [Green Version]
- Novelli, E.M.; Little-Ihrig, L.; Knupp, H.E.; Rogers, N.M.; Yao, M.; Baust, J.J.; Meijles, D.; St Croix, C.M.; Ross, M.A.; Pagano, P.J.; et al. Vascular TSP1-CD47 signaling promotes sickle cell-associated arterial vasculopathy and pulmonary hypertension in mice. Am. J. Physiol. Lung. Cell. Mol. Physiol. 2019, 316, L1150–L1164. [Google Scholar] [CrossRef]
- Wernig, G.; Chen, S.Y.; Cui, L.; Van Neste, C.; Tsai, J.M.; Kambham, N.; Vogel, H.; Natkunam, Y.; Gilliland, D.G.; Nolan, G.; et al. Unifying mechanism for different fibrotic diseases. Proc. Natl. Acad. Sci. USA 2017, 114, 4757–4762. [Google Scholar] [CrossRef] [Green Version]
- Leeming, D.J.; Genovese, F.; Sand, J.M.B.; Rasmussen, D.G.K.; Christiansen, C.; Jenkins, G.; Maher, T.M.; Vestbo, J.; Karsdal, M.A. Can biomarkers of extracellular matrix remodelling and wound healing be used to identify high risk patients infected with SARS-CoV-2?: Lessons learned from pulmonary fibrosis. Respir. Res. 2021, 22, 38. [Google Scholar] [CrossRef] [PubMed]
- Soto-Pantoja, D.R.; Stein, E.V.; Rogers, N.M.; Sharifi-Sanjani, M.; Isenberg, J.S.; Roberts, D.D. Therapeutic opportunities for targeting the ubiquitous cell surface receptor CD47. Expert. Opin. Ther. Targets. 2013, 17, 89–103. [Google Scholar] [CrossRef] [Green Version]
- Rogers, N.M.; Ghimire, K.; Calzada, M.J.; Isenberg, J.S. Matricellular protein thrombospondin-1 in pulmonary hypertension: Multiple pathways to disease. Cardiovasc. Res. 2017, 113, 858–868. [Google Scholar] [CrossRef] [Green Version]
- Cruz Rodriguez, J.B.; Lange, R.A.; Mukherjee, D. Gamut of cardiac manifestations and complications of COVID-19: A contemporary review. J. Investig. Med. 2020, 68, 1334–1340. [Google Scholar] [CrossRef]
- Fabrizi, F.; Alfieri, C.M.; Cerutti, R.; Lunghi, G.; Messa, P. COVID-19 and Acute Kidney Injury: A Systematic Review and Meta-Analysis. Pathogens 2020, 9, 1052. [Google Scholar] [CrossRef]
- Karmouty-Quintana, H.; Thandavarayan, R.A.; Keller, S.P.; Sahay, S.; Pandit, L.M.; Akkanti, B. Emerging Mechanisms of Pulmonary Vasoconstriction in SARS-CoV-2-Induced Acute Respiratory Distress Syndrome (ARDS) and Potential Therapeutic Targets. Int. J. Mol. Sci. 2020, 21, 8081. [Google Scholar] [CrossRef] [PubMed]
- Scutelnic, A.; Heldner, M.R. Vascular Events, Vascular Disease and Vascular Risk Factors-Strongly Intertwined with COVID-19. Curr. Treat. Options Neurol. 2020, 22, 40. [Google Scholar] [CrossRef]
- Sanghvi, S.K.; Schwarzman, L.S.; Nazir, N.T. Cardiac MRI and Myocardial Injury in COVID-19: Diagnosis, Risk Stratification and Prognosis. Diagnostics 2021, 11, 130. [Google Scholar] [CrossRef] [PubMed]
- Maile, L.A.; Capps, B.E.; Miller, E.C.; Aday, A.W.; Clemmons, D.R. Integrin-associated protein association with SRC homology 2 domain containing tyrosine phosphatase substrate 1 regulates igf-I signaling in vivo. Diabetes 2008, 57, 2637–2643. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Allen, L.B.; Capps, B.E.; Miller, E.C.; Clemmons, D.R.; Maile, L.A. Glucose-oxidized low-density lipoproteins enhance insulin-like growth factor I-stimulated smooth muscle cell proliferation by inhibiting integrin-associated protein cleavage. Endocrinology 2009, 150, 1321–1329. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maile, L.A.; Allen, L.B.; Veluvolu, U.; Capps, B.E.; Busby, W.H.; Rowland, M.; Clemmons, D.R. Identification of compounds that inhibit IGF-I signaling in hyperglycemia. Exp. Diabetes Res. 2009, 2009, 267107. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maile, L.A.; Allen, L.B.; Hanzaker, C.F.; Gollahon, K.A.; Dunbar, P.; Clemmons, D.R. Glucose regulation of thrombospondin and its role in the modulation of smooth muscle cell proliferation. Exp. Diabetes Res. 2010, 2010, 617052. [Google Scholar] [CrossRef] [Green Version]
- Maile, L.A.; Gollahon, K.; Wai, C.; Byfield, G.; Hartnett, M.E.; Clemmons, D. Disruption of the association of integrin-associated protein (IAP) with tyrosine phosphatase non-receptor type substrate-1 (SHPS)-1 inhibits pathophysiological changes in retinal endothelial function in a rat model of diabetes. Diabetologia 2012, 55, 835–844. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abdul-Rahman, O.; Sasvari-Szekely, M.; Ver, A.; Rosta, K.; Szasz, B.K.; Kereszturi, E.; Keszler, G. Altered gene expression profiles in the hippocampus and prefrontal cortex of type 2 diabetic rats. BMC Genom. 2012, 13, 81. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abu El-Asrar, A.M.; Nawaz, M.I.; Ola, M.S.; De Hertogh, G.; Opdenakker, G.; Geboes, K. Expression of thrombospondin-2 as a marker in proliferative diabetic retinopathy. Acta Ophthalmol. 2013, 91, e169–e177. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.M.; Tao, J.; Chen, D.D.; Cai, J.J.; Irani, K.; Wang, Q.; Yuan, H.; Chen, A.F. MicroRNA miR-27b rescues bone marrow-derived angiogenic cell function and accelerates wound healing in type 2 diabetes mellitus. Arterioscler. Thromb. Vasc. Biol. 2014, 34, 99–109. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bitar, M.S. Diabetes Impairs Angiogenesis and Induces Endothelial Cell Senescence by Up-Regulating Thrombospondin-CD47-Dependent Signaling. Int. J. Mol. Sci. 2019, 20, 673. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maimaitiyiming, H.; Norman, H.; Zhou, Q.; Wang, S. CD47 deficiency protects mice from diet-induced obesity and improves whole body glucose tolerance and insulin sensitivity. Sci. Rep. 2015, 5, 8846. [Google Scholar] [CrossRef] [Green Version]
- Norman-Burgdolf, H.; Li, D.; Sullivan, P.; Wang, S. CD47 differentially regulates white and brown fat function. Biol. Open. 2020, 9, bio056747. [Google Scholar] [CrossRef]
- Cooper, D.K.C.; Hara, H.; Iwase, H.; Yamamoto, T.; Li, Q.; Ezzelarab, M.; Federzoni, E.; Dandro, A.; Ayares, D. Justification of specific genetic modifications in pigs for clinical organ xenotransplantation. Xenotransplantation 2019, 26, e12516. [Google Scholar] [CrossRef]
- Hosny, N.; Matson, A.W.; Kumbha, R.; Steinhoff, M.; Sushil Rao, J.; El-Abaseri, T.B.; Sabek, N.A.; Mahmoud, M.A.; Hering, B.J.; Burlak, C. 3’UTR enhances hCD47 cell surface expression, self-signal function, and reduces ER stress in porcine fibroblasts. Xenotransplantation 2021, 28, e12641. [Google Scholar] [CrossRef]
- Feng, R.; Zhao, H.; Xu, J.; Shen, C. CD47: The next checkpoint target for cancer immunotherapy. Crit. Rev. Oncol. Hematol. 2020, 152, 103014. [Google Scholar] [CrossRef]
- Oronsky, B.; Knox, S.; Cabrales, P.; Oronsky, A.; Reid, T.R. Desperate Times, Desperate Measures: The Case for RRx-001 in the Treatment of COVID-19. Semin. Oncol. 2020, 47, 305–308. [Google Scholar] [CrossRef]
- Huang, F.; Yang, C.; Yu, W.; Bi, Y.; Long, F.; Wang, J.; Li, Y.; Jing, S. Hepatitis E virus infection activates signal regulator protein alpha to down-regulate type I interferon. Immunol. Res. 2016, 64, 115–122. [Google Scholar] [CrossRef]
- Roquilly, A.; Jacqueline, C.; Davieau, M.; Mollé, A.; Sadek, A.; Fourgeux, C.; Rooze, P.; Broquet, A.; Misme-Aucouturier, B.; Chaumette, T.; et al. Alveolar macrophages are epigenetically altered after inflammation, leading to long-term lung immunoparalysis. Nat. Immunol. 2020, 21, 636–648. [Google Scholar] [CrossRef] [PubMed]
- Saheb Sharif-Askari, N.; Saheb Sharif-Askari, F.; Mdkhana, B.; Al Heialy, S.; Alsafar, H.S.; Hamoudi, R.; Hamid, Q.; Halwani, R. Enhanced expression of immune checkpoint receptors during SARS-CoV-2 viral infection. Mol. Ther. Methods. Clin. Dev. 2021, 20, 109–121. [Google Scholar] [CrossRef] [PubMed]
- Filbin, M.R.; Mehta, A.; Schneider, A.M.; Kays, K.R.; Guess, J.R.; Gentili, M.; Fenyves, B.G.; Charland, N.C.; Gonye, A.L.K.; Gushterova, I.; et al. Longitudinal proteomic analysis of severe COVID-19 reveals survival-associated signatures, tissue-specific cell death, and cell-cell interactions. Cell. Rep. Med. 2021, 2, 100287. [Google Scholar] [CrossRef] [PubMed]
- Boyapati, A.; Wipperman, M.F.; Ehmann, P.J.; Hamon, S.; Lederer, D.J.; Waldron, A.; Flanagan, J.J.; Karayusuf, E.; Bhore, R.; Nivens, M.C.; et al. Baseline SARS-CoV-2 Viral Load is Associated With COVID-19 Disease Severity and Clinical Outcomes: Post-Hoc Analyses of a Phase 2/3 Trial. J. Infect. Dis. 2021, jiab445. [Google Scholar] [CrossRef]
- Chen, P.Z.; Bobrovitz, N.; Premji, Z.; Koopmans, M.; Fisman, D.N.; Gu, F.X. SARS-CoV-2 shedding dynamics across the respiratory tract, sex, and disease severity for adult and pediatric COVID-19. Elife 2021, 10, e70458. [Google Scholar] [CrossRef]
- Merad, M.; Martin, J.C. Pathological inflammation in patients with COVID-19: A key role for monocytes and macrophages. Nat. Rev. Immunol. 2020, 20, 355–362. [Google Scholar] [CrossRef]
- Mallapaty, S. Kids and COVID: Why young immune systems are still on top. Nature 2021, 597, 166–168. [Google Scholar] [CrossRef]
- Kuo, T.C.; Chen, A.; Harrabi, O.; Sockolosky, J.T.; Zhang, A.; Sangalang, E.; Doyle, L.V.; Kauder, S.E.; Fontaine, D.; Bollini, S.; et al. Targeting the myeloid checkpoint receptor SIRPα potentiates innate and adaptive immune responses to promote anti-tumor activity. J. Hematol. Oncol. 2020, 13, 160. [Google Scholar] [CrossRef] [PubMed]
Reference | Link between Aging and/or Hypertension and Increased CD47 Levels |
---|---|
[33] | CD47 downregulation may be involved in the alpha-tocopherol-mediated inhibition of age-associated streptococcus pneumoniae lung infection in mice |
[37] | Blocking thrombospondin-1/CD47 signaling alleviates deleterious effects of aging on tissue responses to ischemia |
[38] | CD47 null mice indicate that CD47 functions as a vasopressor |
[39] | CD47-null mice are leaner—loss of signaling from the TSP1-CD47 system promotes the accumulation of normally functioning mitochondria in a tissue-specific and age-dependent fashion, leading to enhanced physical performance, lower reactive oxygen species production, and more efficient metabolism |
[40] | High CD47 levels promote pulmonary arterial hypertension in the lungs from humans and mice |
[41] | TSP1-CD47 signaling is upregulated in clinical pulmonary hypertension and contributes to pulmonary arterial vasculopathy and dysfunction |
[42] | Increased THBS1/CD47 signaling contributes to reduced skin blood flow and wound healing in aged mice |
[43] | CD47 blocks NO-mediated vasodilatation |
[44] | THBS1/CD47 signaling drives endothelial cell senescence |
[45] | TSP1 promotes ageing-associated human and mouse endothelial cell senescence through CD47 |
[46] | Increased CD47 expression causes age-associated deterioration in angiogenesis, blood flow, and glucose homeostasis |
[47] | Increased CD47 levels in the lung of a sickle cell disease patient with pulmonary arterial hypertension relative to control tissues |
[48] | Pulmonary hypertension reduced in a CD47-null mouse model of sickle cell disease |
[49] | Anti-CD47 antibodies reversed fibrosis in various organs in mouse models |
Reference | Link between Aging and/ or Hypertension and Increased CD47 Levels |
---|---|
[58] | Hyperglycemia protects CD47 from cleavage |
[59] | Hyperglycemia protects CD47 from cleavage |
[60] | Hyperglycemia protects CD47 from cleavage |
[61] | Hyperglycemia protects CD47 from cleavage |
[62] | CD47 is involved in pathophysiological changes in retinal cells in response to hyperglycemia in cell cultures and rats |
[63] | Elevated CD47 mRNA levels both in the hippocampus and prefrontal cortex of a type-2 diabetes rat model |
[64] | Increased levels of CD47 in epiretinal membranes with active neovascularization in proliferative diabetic retinopathy |
[65] | Increased THBS1/CD47 signaling in bone marrow-derived angiogenic cells in a rat diabetes model |
[66] | Increased diabetes-associated CD47 levels inhibit angiogenesis and wound healing in a diabetes model in rats |
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McLaughlin, K.-M.; Bojkova, D.; Kandler, J.D.; Bechtel, M.; Reus, P.; Le, T.; Rothweiler, F.; Wagner, J.U.G.; Weigert, A.; Ciesek, S.; et al. A Potential Role of the CD47/SIRPalpha Axis in COVID-19 Pathogenesis. Curr. Issues Mol. Biol. 2021, 43, 1212-1225. https://doi.org/10.3390/cimb43030086
McLaughlin K-M, Bojkova D, Kandler JD, Bechtel M, Reus P, Le T, Rothweiler F, Wagner JUG, Weigert A, Ciesek S, et al. A Potential Role of the CD47/SIRPalpha Axis in COVID-19 Pathogenesis. Current Issues in Molecular Biology. 2021; 43(3):1212-1225. https://doi.org/10.3390/cimb43030086
Chicago/Turabian StyleMcLaughlin, Katie-May, Denisa Bojkova, Joshua D. Kandler, Marco Bechtel, Philipp Reus, Trang Le, Florian Rothweiler, Julian U. G. Wagner, Andreas Weigert, Sandra Ciesek, and et al. 2021. "A Potential Role of the CD47/SIRPalpha Axis in COVID-19 Pathogenesis" Current Issues in Molecular Biology 43, no. 3: 1212-1225. https://doi.org/10.3390/cimb43030086
APA StyleMcLaughlin, K. -M., Bojkova, D., Kandler, J. D., Bechtel, M., Reus, P., Le, T., Rothweiler, F., Wagner, J. U. G., Weigert, A., Ciesek, S., Wass, M. N., Michaelis, M., & Cinatl, J., Jr. (2021). A Potential Role of the CD47/SIRPalpha Axis in COVID-19 Pathogenesis. Current Issues in Molecular Biology, 43(3), 1212-1225. https://doi.org/10.3390/cimb43030086