Artesunate: A natural product-based immunomodulator involved in human complement - 19/02/21
, Ying Jie Ma a, ⁎ , Peter Garred aBienvenue sur EM-consulte, la référence des professionnels de santé.
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Graphical abstract |
Highlights |
• | ART possesses anti-complement bioactivities. |
• | ART is involved in three effector pathways of complement interception. |
• | ART targets C1q likely via binding of C1q globular head region. |
• | ART specifically binds to the key therapeutic targets of C1q, C3 and C5. |
• | A modified ELISA selectively allows the effector pathways of complement activation. |
Abstract |
Complement is an important innate immune defence machinery. Once dysregulated, it is often linked to pathogenesis of diverse autoimmune diseases. Artesunate (ART) is a well-known anti-malarial compound. Recently, ART has been highlighted by its potential therapeutic effects on certain complement-related autoimmune diseases. However, the underlying mechanisms are hitherto unknown. In the present study, we found that ART mediated complement interception as validated by analysis of complement haemolytic assay. In cell-based setup using dying Jurkat cells, ART-mediated complement interception was also confirmed. Further, we newly established an ELISA system selectively allowing complement activation via the classical pathway, the lectin pathway and the alternative pathway, respectively. ELISA analysis revealed that ART dose-dependently inhibited C4 activation, C3 activation and terminal complement complex assembly via the effector pathways. ART was found to blockade C1q, C3 and C5 with a lesser extent to properdin. The interaction of ART with C1q was determined to be mediated via C1q globular head region. FACS analysis using ART-conjugated mesoporous silica particles revealed that ART specifically bound the key therapeutic targets of C1q, C3 and C5 on microparticles. In conclusion, we for the first time report the anti-complement bioactivities of ART and suggest a potential therapeutic benefit of ART in the complement-related human diseases.
Le texte complet de cet article est disponible en PDF.Abbreviations : aHUS, AMD, AP, ART, ART@MSM, C1q-Dpl, C3-Dpl, C5-Dpl, CL-10 or CL-L1, CL-11 or CL-K1, CL-12 or CL-P1, CL-LK, CP, CRP, Es, EDC, FCS, fP-Def, FSC, GlcNAc, GMFI, IR, LP, mAb, MASPs, MBL, MBL-Def, MSM, NH2@MSM, NHS, PEI, PI, PNH, PRMs, PTX3, RA, SAP, SEM, sEs, SLE, SSC, TCC, TCM, WHO
Keywords : Artesunate, Anti-complement activity, Complement regulation, Complement assay, Mesoporous silica particles
Plan
Vol 136
Article 111234- avril 2021 Retour au numéro
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