SARS‐CoV‐2 triggers complement activation through interactions with heparan sulfate
Objectives To determine whether SARS‐CoV‐2 can trigger complement activation, the pathways that are involved and the functional significance of the resultant effect. Methods SARS‐CoV‐2 was inoculated into a human lepirudin‐anticoagulated whole blood model, which contains a full repertoire of complem...
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Published in | Clinical & translational immunology Vol. 11; no. 8; pp. e1413 - n/a |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Milton, Queensland
John Wiley & Sons, Inc
2022
John Wiley and Sons Inc Wiley |
Subjects | |
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Abstract | Objectives
To determine whether SARS‐CoV‐2 can trigger complement activation, the pathways that are involved and the functional significance of the resultant effect.
Methods
SARS‐CoV‐2 was inoculated into a human lepirudin‐anticoagulated whole blood model, which contains a full repertoire of complement factors and leukocytes that express complement receptors. Complement activation was determined by measuring C5a production with an ELISA, and pretreatment with specific inhibitors was used to identify the pathways involved. The functional significance of this was then assessed by measuring markers of C5a signalling including leukocyte C5aR1 internalisation and CD11b upregulation with flow cytometry.
Results
SARS‐CoV‐2 inoculation in this whole blood model caused progressive C5a production over 24 h, which was significantly reduced by inhibitors for factor B, C3, C5 and heparan sulfate. However, this phenomenon could not be replicated in cell‐free plasma, highlighting the requirement for cell surface interactions with heparan sulfate. Functional analysis of this phenomenon revealed that C5aR1 signalling and CD11b upregulation in granulocytes and monocytes was delayed and only occurred after 24 h.
Conclusion
SARS‐CoV‐2 is a noncanonical alternative pathway activator that progressively triggers complement activation through interactions with heparan sulfate.
The mechanisms by which SARS‐CoV‐2 activates complement remain unclear, and so here, we utilised an ex vivo human whole blood model to interrogate the pathways and functional responses involved. SARS‐CoV‐2 inoculation in blood caused progressive C5a production over 24 h, which was blocked entirely by inhibitors for factor B, C3, C5 and heparan sulfate. This study therefore provides direct mechanistic evidence for SARS‐CoV‐2 driving complement activation and the requirement for cell surfaces and heparan sulfate. |
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AbstractList | Objectives
To determine whether SARS‐CoV‐2 can trigger complement activation, the pathways that are involved and the functional significance of the resultant effect.
Methods
SARS‐CoV‐2 was inoculated into a human lepirudin‐anticoagulated whole blood model, which contains a full repertoire of complement factors and leukocytes that express complement receptors. Complement activation was determined by measuring C5a production with an ELISA, and pretreatment with specific inhibitors was used to identify the pathways involved. The functional significance of this was then assessed by measuring markers of C5a signalling including leukocyte C5aR1 internalisation and CD11b upregulation with flow cytometry.
Results
SARS‐CoV‐2 inoculation in this whole blood model caused progressive C5a production over 24 h, which was significantly reduced by inhibitors for factor B, C3, C5 and heparan sulfate. However, this phenomenon could not be replicated in cell‐free plasma, highlighting the requirement for cell surface interactions with heparan sulfate. Functional analysis of this phenomenon revealed that C5aR1 signalling and CD11b upregulation in granulocytes and monocytes was delayed and only occurred after 24 h.
Conclusion
SARS‐CoV‐2 is a noncanonical alternative pathway activator that progressively triggers complement activation through interactions with heparan sulfate.
The mechanisms by which SARS‐CoV‐2 activates complement remain unclear, and so here, we utilised an ex vivo human whole blood model to interrogate the pathways and functional responses involved. SARS‐CoV‐2 inoculation in blood caused progressive C5a production over 24 h, which was blocked entirely by inhibitors for factor B, C3, C5 and heparan sulfate. This study therefore provides direct mechanistic evidence for SARS‐CoV‐2 driving complement activation and the requirement for cell surfaces and heparan sulfate. The mechanisms by which SARS‐CoV‐2 activates complement remain unclear, and so here, we utilised an ex vivo human whole blood model to interrogate the pathways and functional responses involved. SARS‐CoV‐2 inoculation in blood caused progressive C5a production over 24 h, which was blocked entirely by inhibitors for factor B, C3, C5 and heparan sulfate. This study therefore provides direct mechanistic evidence for SARS‐CoV‐2 driving complement activation and the requirement for cell surfaces and heparan sulfate. ObjectivesTo determine whether SARS‐CoV‐2 can trigger complement activation, the pathways that are involved and the functional significance of the resultant effect.MethodsSARS‐CoV‐2 was inoculated into a human lepirudin‐anticoagulated whole blood model, which contains a full repertoire of complement factors and leukocytes that express complement receptors. Complement activation was determined by measuring C5a production with an ELISA, and pretreatment with specific inhibitors was used to identify the pathways involved. The functional significance of this was then assessed by measuring markers of C5a signalling including leukocyte C5aR1 internalisation and CD11b upregulation with flow cytometry.ResultsSARS‐CoV‐2 inoculation in this whole blood model caused progressive C5a production over 24 h, which was significantly reduced by inhibitors for factor B, C3, C5 and heparan sulfate. However, this phenomenon could not be replicated in cell‐free plasma, highlighting the requirement for cell surface interactions with heparan sulfate. Functional analysis of this phenomenon revealed that C5aR1 signalling and CD11b upregulation in granulocytes and monocytes was delayed and only occurred after 24 h.ConclusionSARS‐CoV‐2 is a noncanonical alternative pathway activator that progressively triggers complement activation through interactions with heparan sulfate. Abstract Objectives To determine whether SARS‐CoV‐2 can trigger complement activation, the pathways that are involved and the functional significance of the resultant effect. Methods SARS‐CoV‐2 was inoculated into a human lepirudin‐anticoagulated whole blood model, which contains a full repertoire of complement factors and leukocytes that express complement receptors. Complement activation was determined by measuring C5a production with an ELISA, and pretreatment with specific inhibitors was used to identify the pathways involved. The functional significance of this was then assessed by measuring markers of C5a signalling including leukocyte C5aR1 internalisation and CD11b upregulation with flow cytometry. Results SARS‐CoV‐2 inoculation in this whole blood model caused progressive C5a production over 24 h, which was significantly reduced by inhibitors for factor B, C3, C5 and heparan sulfate. However, this phenomenon could not be replicated in cell‐free plasma, highlighting the requirement for cell surface interactions with heparan sulfate. Functional analysis of this phenomenon revealed that C5aR1 signalling and CD11b upregulation in granulocytes and monocytes was delayed and only occurred after 24 h. Conclusion SARS‐CoV‐2 is a noncanonical alternative pathway activator that progressively triggers complement activation through interactions with heparan sulfate. |
Author | Lee, John D Ferro, Vito Modhiran, Naphak Albornoz, Eduardo A Amarilla, Alberto A Chhabra, Mohit Khromykh, Alexander A Woodruff, Trent M Clark, Richard J Watterson, Daniel Lo, Martin W |
AuthorAffiliation | 3 Australian Infectious Diseases Research Centre Global Virus Network Centre of Excellence Brisbane QLD Australia 1 School of Biomedical Sciences, Faculty of Medicine University of Queensland Brisbane QLD Australia 2 School of Chemistry and Molecular Biosciences University of Queensland Brisbane QLD Australia |
AuthorAffiliation_xml | – name: 3 Australian Infectious Diseases Research Centre Global Virus Network Centre of Excellence Brisbane QLD Australia – name: 2 School of Chemistry and Molecular Biosciences University of Queensland Brisbane QLD Australia – name: 1 School of Biomedical Sciences, Faculty of Medicine University of Queensland Brisbane QLD Australia |
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CitedBy_id | crossref_primary_10_1016_j_biopha_2023_115294 crossref_primary_10_3390_ijms25137209 crossref_primary_10_1002_prca_202200070 crossref_primary_10_1002_pro_4843 crossref_primary_10_1126_scitranslmed_adi0252 crossref_primary_10_1007_s42977_023_00153_8 crossref_primary_10_1038_s44318_024_00061_0 crossref_primary_10_3390_cimb45060330 crossref_primary_10_3389_fimmu_2024_1337070 crossref_primary_10_3389_fimmu_2024_1281263 crossref_primary_10_1016_j_imbio_2023_152393 crossref_primary_10_1016_j_isci_2023_108095 crossref_primary_10_1016_j_it_2024_04_001 crossref_primary_10_1007_s12033_024_01096_8 |
Cites_doi | 10.1016/j.it.2020.09.008 10.1016/j.clim.2021.108716 10.1016/j.ijid.2020.08.004 10.1126/sciimmunol.abg0833 10.1126/sciimmunol.abh2259 10.1056/NEJMcp2009575 10.4049/jimmunol.2000644 10.1016/j.molimm.2014.08.005 10.3389/fimmu.2021.742446 10.1182/blood.2020008248 10.3389/fimmu.2020.580641 10.3389/fimmu.2021.714511 10.1136/bmj.m1443 10.1016/j.bcp.2020.114156 10.1016/j.jaut.2021.102595 10.1002/cti2.1269 10.1128/mBio.01755-17 10.1016/j.cell.2020.09.033 10.1038/s41591-020-1021-2 10.1016/j.smim.2022.101604 10.3389/fmicb.2021.625136 10.1101/cshperspect.a004952 10.3390/v13020304 10.1016/j.ijbiomac.2021.10.112 10.1126/science.abc6027 10.4049/jimmunol.1001819 10.1016/S1473-3099(20)30120-1 10.1021/acs.bioconjchem.1c00453 10.3389/fimmu.2021.767981 10.1055/s-0040-1715835 |
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References | 2021; 6 2020; 20 2020; 383 2020; 41 2020; 120 2020; 180 2021; 226 2020; 183 2020; 369 2010; 185 2020; 205 2020; 11 2020; 99 2011; 3 2021; 13 2018; 9 2021; 32 2021; 10 2021; 12 2021; 117 2015; 63 2022; 12 2021; 193 2020; 26 2020; 136 e_1_2_9_30_1 e_1_2_9_31_1 e_1_2_9_11_1 e_1_2_9_10_1 e_1_2_9_13_1 e_1_2_9_12_1 e_1_2_9_15_1 e_1_2_9_14_1 e_1_2_9_17_1 e_1_2_9_16_1 e_1_2_9_19_1 e_1_2_9_18_1 e_1_2_9_20_1 e_1_2_9_22_1 e_1_2_9_21_1 e_1_2_9_24_1 e_1_2_9_23_1 e_1_2_9_8_1 e_1_2_9_7_1 e_1_2_9_6_1 e_1_2_9_5_1 e_1_2_9_4_1 e_1_2_9_3_1 e_1_2_9_2_1 e_1_2_9_9_1 e_1_2_9_26_1 e_1_2_9_25_1 e_1_2_9_28_1 e_1_2_9_27_1 e_1_2_9_29_1 |
References_xml | – volume: 183 start-page: 1043 year: 2020 end-page: 1057 article-title: SARS‐CoV‐2 infection depends on cellular heparan sulfate and ACE2 publication-title: Cell – volume: 205 start-page: 1488 year: 2020 end-page: 1495 article-title: COVID‐19: complement, coagulation, and collateral damage publication-title: J Immunol – volume: 6 year: 2021 article-title: SARS‐CoV‐2 drives JAK1/2‐dependent local complement hyperactivation publication-title: Sci Immunol – volume: 99 start-page: 381 year: 2020 end-page: 385 article-title: Increased complement receptor‐3 levels in monocytes and granulocytes distinguish COVID‐19 patients with pneumonia from those with mild symptoms publication-title: Int J Infect Dis – volume: 12 year: 2021 article-title: Lectin pathway mediates complement activation by SARS‐CoV‐2 proteins publication-title: Front Immunol – volume: 12 year: 2022 article-title: Application of the C3 inhibitor compstatin in a human whole blood model designed for complement research – 20 years of experience and future perspectives publication-title: Semin Immunol – volume: 9 year: 2018 article-title: Complement C5a receptor 1 exacerbates the pathophysiology of sepsis and is a potential target for disease treatment publication-title: mBio – volume: 26 start-page: 1609 year: 2020 end-page: 1615 article-title: Immune complement and coagulation dysfunction in adverse outcomes of SARS‐CoV‐2 infection publication-title: Nat Med – volume: 12 year: 2021 article-title: An optimized high‐throughput Immuno‐plaque assay for SARS‐CoV‐2 publication-title: Front Microbiol – volume: 41 start-page: 965 year: 2020 end-page: 967 article-title: The complement C5a‐C5aR1 GPCR axis in COVID‐19 therapeutics publication-title: Trends Immunol – volume: 63 start-page: 203 year: 2015 end-page: 208 article-title: The role of heparan sulfate as determining pathogenic factor in complement factor H‐associated diseases publication-title: Mol Immunol – volume: 10 year: 2021 article-title: Preclinical development of a molecular clamp‐stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2 publication-title: Clin Transl Immunology – volume: 369 year: 2020 article-title: Viral load dynamics and disease severity in patients infected with SARS‐CoV‐2 in Zhejiang province, China, January‐March 2020: retrospective cohort study publication-title: BMJ – volume: 226 year: 2021 article-title: Activation of classical and alternative complement pathways in the pathogenesis of lung injury in COVID‐19 publication-title: Clin Immunol – volume: 11 start-page: 580641 year: 2020 article-title: Covid‐19: perspectives on innate immune evasion publication-title: Front Immunol – volume: 32 start-page: 2420 year: 2021 end-page: 2431 article-title: Development of improved synthetic routes to Pixatimod (PG545), a sulfated oligosaccharide‐steroid conjugate publication-title: Bioconjug Chem – volume: 120 start-page: 1720 year: 2020 end-page: 1724 article-title: Mannose‐binding lectin is associated with thrombosis and coagulopathy in critically ill COVID‐19 patients publication-title: J Thromb Haemost – volume: 3 year: 2011 article-title: Heparan sulfate proteoglycans publication-title: Cold Spring Harb Perspect Biol – volume: 117 year: 2021 article-title: Chromosome 3 cluster rs11385942 variant links complement activation with severe COVID‐19 publication-title: J Autoimmun – volume: 180 year: 2020 article-title: Pharmacological characterisation of small molecule C5aR1 inhibitors in human cells reveals biased activities for signalling and function publication-title: Biochem Pharmacol – volume: 193 start-page: 1124 year: 2021 end-page: 1129 article-title: SARS‐CoV‐2 spike protein causes blood coagulation and thrombosis by competitive binding to heparan sulfate publication-title: Int J Biol Macromol – volume: 383 start-page: 2451 year: 2020 end-page: 2460 article-title: Severe Covid‐19 publication-title: N Engl J Med – volume: 20 start-page: 533 year: 2020 end-page: 534 article-title: An interactive web‐based dashboard to track COVID‐19 in real time publication-title: Lancet Infect Dis – volume: 136 start-page: 2080 year: 2020 end-page: 2089 article-title: Direct activation of the alternative complement pathway by SARS‐CoV‐2 spike proteins is blocked by factor D inhibition publication-title: Blood – volume: 6 year: 2021 article-title: Increased complement activation is a distinctive feature of severe SARS‐CoV‐2 infection publication-title: Sci Immunol – volume: 13 start-page: 304 year: 2021 article-title: Relationships between viral load and the clinical course of COVID‐19 publication-title: Viruses – volume: 12 year: 2021 article-title: SARS‐CoV‐2 antibodies mediate complement and cellular driven inflammation publication-title: Front Immunol – volume: 185 start-page: 4169 year: 2010 end-page: 4178 article-title: Selective inhibition of the lectin pathway of complement with phage display selected peptides against mannose‐binding lectin‐associated serine protease (MASP)‐1 and ‐2: significant contribution of MASP‐1 to lectin pathway activation publication-title: J Immunol – volume: 369 start-page: 718 year: 2020 end-page: 724 article-title: Impaired type I interferon activity and inflammatory responses in severe COVID‐19 patients publication-title: Science – volume: 12 year: 2021 article-title: Complement alternative and mannose‐binding lectin pathway activation is associated with COVID‐19 mortality publication-title: Front Immunol – ident: e_1_2_9_7_1 doi: 10.1016/j.it.2020.09.008 – ident: e_1_2_9_8_1 doi: 10.1016/j.clim.2021.108716 – ident: e_1_2_9_10_1 doi: 10.1016/j.ijid.2020.08.004 – ident: e_1_2_9_12_1 doi: 10.1126/sciimmunol.abg0833 – ident: e_1_2_9_9_1 doi: 10.1126/sciimmunol.abh2259 – ident: e_1_2_9_5_1 doi: 10.1056/NEJMcp2009575 – ident: e_1_2_9_6_1 doi: 10.4049/jimmunol.2000644 – ident: e_1_2_9_23_1 doi: 10.1016/j.molimm.2014.08.005 – ident: e_1_2_9_17_1 doi: 10.3389/fimmu.2021.742446 – ident: e_1_2_9_18_1 doi: 10.1182/blood.2020008248 – ident: e_1_2_9_3_1 doi: 10.3389/fimmu.2020.580641 – ident: e_1_2_9_19_1 doi: 10.3389/fimmu.2021.714511 – ident: e_1_2_9_21_1 doi: 10.1136/bmj.m1443 – ident: e_1_2_9_30_1 doi: 10.1016/j.bcp.2020.114156 – ident: e_1_2_9_13_1 doi: 10.1016/j.jaut.2021.102595 – ident: e_1_2_9_31_1 doi: 10.1002/cti2.1269 – ident: e_1_2_9_11_1 doi: 10.1128/mBio.01755-17 – ident: e_1_2_9_24_1 doi: 10.1016/j.cell.2020.09.033 – ident: e_1_2_9_15_1 doi: 10.1038/s41591-020-1021-2 – ident: e_1_2_9_20_1 doi: 10.1016/j.smim.2022.101604 – ident: e_1_2_9_27_1 doi: 10.3389/fmicb.2021.625136 – ident: e_1_2_9_25_1 doi: 10.1101/cshperspect.a004952 – ident: e_1_2_9_22_1 doi: 10.3390/v13020304 – ident: e_1_2_9_26_1 doi: 10.1016/j.ijbiomac.2021.10.112 – ident: e_1_2_9_4_1 doi: 10.1126/science.abc6027 – ident: e_1_2_9_28_1 doi: 10.4049/jimmunol.1001819 – ident: e_1_2_9_2_1 doi: 10.1016/S1473-3099(20)30120-1 – ident: e_1_2_9_29_1 doi: 10.1021/acs.bioconjchem.1c00453 – ident: e_1_2_9_16_1 doi: 10.3389/fimmu.2021.767981 – ident: e_1_2_9_14_1 doi: 10.1055/s-0040-1715835 |
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To determine whether SARS‐CoV‐2 can trigger complement activation, the pathways that are involved and the functional significance of the resultant... ObjectivesTo determine whether SARS‐CoV‐2 can trigger complement activation, the pathways that are involved and the functional significance of the resultant... ObjectivesTo determine whether SARS-CoV-2 can trigger complement activation, the pathways that are involved and the functional significance of the resultant... The mechanisms by which SARS‐CoV‐2 activates complement remain unclear, and so here, we utilised an ex vivo human whole blood model to interrogate the pathways... Abstract Objectives To determine whether SARS‐CoV‐2 can trigger complement activation, the pathways that are involved and the functional significance of the... |
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SubjectTerms | Alternative pathway CD11b antigen Cell surface complement Complement activation Complement component C3 Complement component C5a Complement receptors coronavirus Coronaviruses COVID-19 Drug dosages Flow cytometry Heparan sulfate Infections Inoculation Investigations Lectins leukocyte activation Leukocytes (granulocytic) Monocytes Neutrophils Plasma Proteins SARS‐CoV‐2 Severe acute respiratory syndrome coronavirus 2 Short Communication Signal transduction |
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Title | SARS‐CoV‐2 triggers complement activation through interactions with heparan sulfate |
URI | https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fcti2.1413 https://www.proquest.com/docview/2707499388 https://search.proquest.com/docview/2706182683 https://pubmed.ncbi.nlm.nih.gov/PMC9387400 https://doaj.org/article/fce3333fc3fd462e95eb7a2ae93b9833 |
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