Phagocytosis of live and dead Escherichia coli and Staphylococcus aureus in human whole blood is markedly reduced by combined inhibition of C5aR1 and CD14
Basic science published in Mol Immunol (2019)
Abstract
BACKGROUND: Sepsis is a dysregulated host response to infection. The aim of this study was to investigate the effects of complement- and CD14 inhibition on phagocytosis of live and dead Gram-negative and Gram-positive bacteria in human whole blood. METHODS: Lepirudin-anticoagulated blood was incubated with live or dead E. coli or S. aureus at 37 °C for 120 min with or without the C5aR1 antagonist PMX53 and/or anti-CD14. Granulocyte and monocyte phagocytosis were measured by flow cytometry, and five plasma cytokines by multiplex, yielding a total of 28 mediators of inflammation tested for. RESULTS: 16/28 conditions were reduced by PMX53, 7/28 by anti-CD14, and 24/28 by combined PMX53 and CD14 inhibition. The effect of complement inhibition was quantitatively more pronounced, in particular for the responses to S. aureus. The effect of anti-CD14 was modest, except for a marked reduction in INF-β. The responses to live and dead S. aureus were equally inhibited, whereas the responses to live E. coli were inhibited less than those to dead E. coli. CONCLUSION: C5aR1 inhibited phagocytosis-induced inflammation by live and dead E. coli and S. aureus. CD14 blockade potentiated the effect of C5aR1 blockade, thus attenuating inflammation.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Lepirudin-anticoagulated whole blood model demonstrates combined C5aR1/CD14 inhibition reduces 24/28 phagocytosis-induced inflammatory mediators, supporting clinical anti-inflammatory targeting.
Por qué esto importa para la hirudoterapia
Este estudio examinó cómo la inhibición combinada del receptor del complemento C5aR1 (utilizando PMX53) y de CD14 afecta la fagocitosis de E. coli y S. aureus vivos y muertos en sangre humana total anticoagulada con lepirudina. El bloqueo de C5aR1 redujo la inflamación en 16 de 28 condiciones evaluadas, mientras que la inhibición combinada de C5aR1 y CD14 redujo 24 de 28 condiciones, mostrando la inhibición del complemento un efecto cuantitativamente más pronunciado, particularmente para las respuestas frente a S. aureus. El resumen menciona la lepirudina únicamente como el anticoagulante que permite el modelo de sangre total y no aporta información sobre la biología de la sanguijuela, sustancias derivadas de la sanguijuela ni hirudoterapia. En consecuencia, no puede establecerse ninguna conexión defendible con la hirudoterapia o con el secretoma de la sanguijuela a partir únicamente de este resumen; el estudio se centra en la modulación del complemento y de la inmunidad innata.
Citación
Phagocytosis of live and dead Escherichia coli and Staphylococcus aureus in human whole blood is markedly reduced by combined inhibition of C5aR1 and CD14.
Skjeflo EW et al. · Molecular immunology, 2019
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026