SARS-CoV-2 triggers complement activation through interactions with heparan sulfate
Research article published in Clinical & translational immunology (2022)
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.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
To determine whether SARS-CoV-2 can trigger complement activation, the pathways that are involved and the functional significance of the resultant effect.
Por qué esto importa para la hirudoterapia
Este estudio investigó si el SARS-CoV-2 desencadena la activación del complemento utilizando un modelo de sangre humana total anticoagulada con lepirudina, hallando que el virus activa progresivamente la vía alternativa del complemento mediante interacciones con el heparán sulfato de la superficie celular, lo que conduce a la producción de C5a y a la señalización leucocitaria downstream. La lepirudina, una hirudina recombinante, se menciona únicamente como el reactivo anticoagulante empleado en el modelo de sangre ex vivo y no es en sí misma objeto de investigación. El foco del estudio es la inmunología viral y la biología del complemento. La conexión con el ámbito de ASH es mínima: la lepirudina sirve solo como herramienta experimental, y el estudio no aporta datos relevantes para la hirudoterapia, la biología de la sanguijuela ni las propiedades terapéuticas del secretoma de la sanguijuela.
Citación
SARS-CoV-2 triggers complement activation through interactions with heparan sulfate
Lo MW et al. · Clinical & translational immunology, 2022
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026