Artemisinin inhibits neutrophil and macrophage chemotaxis, cytokine production and NET release.

Autor: Morad HOJ; Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London Bridge, London, SE1 1UL, UK., Luqman S; Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London Bridge, London, SE1 1UL, UK.; Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow, Uttar Pradesh, 226015, India., Pinto LG; Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London Bridge, London, SE1 1UL, UK., Cunningham KP; Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London Bridge, London, SE1 1UL, UK., Vilar B; Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London Bridge, London, SE1 1UL, UK., Clayton G; School of Immunology and Microbial Sciences, King's College London, Guy's Campus, London Bridge, London, SE1 1UL, UK., Shankar-Hari M; The Queen's Medical Research Institute, Edinburgh BioQuarter, Centre for Inflammation Research, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.; Department of Intensive Care Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK., McNaughton PA; Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London Bridge, London, SE1 1UL, UK. peter.mcnaughton@kcl.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Jun 30; Vol. 12 (1), pp. 11078. Date of Electronic Publication: 2022 Jun 30.
DOI: 10.1038/s41598-022-15214-6
Abstrakt: Immune cell chemotaxis to the sites of pathogen invasion is critical for fighting infection, but in life-threatening conditions such as sepsis and Covid-19, excess activation of the innate immune system is thought to cause a damaging invasion of immune cells into tissues and a consequent excessive release of cytokines, chemokines and neutrophil extracellular traps (NETs). In these circumstances, tempering excessive activation of the innate immune system may, paradoxically, promote recovery. Here we identify the antimalarial compound artemisinin as a potent and selective inhibitor of neutrophil and macrophage chemotaxis induced by a range of chemotactic agents. Artemisinin released calcium from intracellular stores in a similar way to thapsigargin, a known inhibitor of the Sarco/Endoplasmic Reticulum Calcium ATPase pump (SERCA), but unlike thapsigargin, artemisinin blocks only the SERCA3 isoform. Inhibition of SERCA3 by artemisinin was irreversible and was inhibited by iron chelation, suggesting iron-catalysed alkylation of a specific cysteine residue in SERCA3 as the mechanism by which artemisinin inhibits neutrophil motility. In murine infection models, artemisinin potently suppressed neutrophil invasion into both peritoneum and lung in vivo and inhibited the release of cytokines/chemokines and NETs. This work suggests that artemisinin may have value as a therapy in conditions such as sepsis and Covid-19 in which over-activation of the innate immune system causes tissue injury that can lead to death.
(© 2022. The Author(s).)
Databáze: MEDLINE
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