dc.contributor.author
Elst, Jessy
dc.contributor.author
Maurer, Marcus
dc.contributor.author
Sabato, Vito
dc.contributor.author
Faber, Margaretha A.
dc.contributor.author
Bridts, Chris H.
dc.contributor.author
Mertens, Christel
dc.contributor.author
Houdt, Michel Van
dc.contributor.author
Gasse, Athina L. Van
dc.contributor.author
Poorten, Marie-Line M. van der
dc.contributor.author
De Puysseleyr, Leander P.
dc.contributor.author
Hagendorens, Margo M.
dc.contributor.author
Tendeloo, Viggo F. Van
dc.contributor.author
Lion, Eva
dc.contributor.author
Campillo-Davo, Diana
dc.contributor.author
Ebo, Didier G.
dc.date.accessioned
2021-11-03T13:24:13Z
dc.date.available
2021-11-03T13:24:13Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/32500
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-32225
dc.description.abstract
Neuromuscular blocking agents (NMBAs) like atracurium and rocuronium as well as fluoroquinolones (FQs) cause mast cell-mediated anaphylaxis by activating Mas-related G protein-coupled receptor X2 (MRGPRX2), but many questions remain unanswered. Here, we address three of them, namely whether primary human mast cells show similar activation by these drugs as murine mast cells and mast cell lines, how sugammadex protects from atracurium-induced MRGPRX2-mediated mast cell activation, and why some but not all patients treated with rocuronium develop anaphylaxis. We used peripheral blood-derived cultured mast cells from healthy donors and patients, assessed mast cell activation and degranulation by quantifying intracellular calcium and CD63 expression, respectively, and made use of MRGPRX2-silencing, via electroporation with Dicer-substrate small interfering RNAs, and single cell flow cytometric analyses. Atracurium, ciprofloxacin, and levofloxacin activated and degranulated primary human mast cells, but only MRGPRX2-positive and not MRGPRX2-negative or -silenced mast cells. Sugammadex attenuated the atracurium-induced and MRGPRX2-mediated activation and degranulation of human mast cells by reducing free atracurium levels. The mast cells of patients with IgE-independent anaphylaxis to rocuronium were similar, in their MRGPRX2 expression and function, to those of patients with IgE-mediated anaphylaxis. These findings further improve our understanding of the role and relevance of MRGPRX2-driven mast cell activation in anaphylactic reactions to NMBAs and FQs and may help to improve their prediction, prevention, and treatment.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
flow cytometry
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Novel Insights on MRGPRX2-Mediated Hypersensitivity to Neuromuscular Blocking Agents And Fluoroquinolones
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
668962
dcterms.bibliographicCitation.doi
10.3389/fimmu.2021.668962
dcterms.bibliographicCitation.journaltitle
Frontiers in Immunology
dcterms.bibliographicCitation.originalpublishername
Frontiers Media SA
dcterms.bibliographicCitation.volume
12
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
34385999
dcterms.isPartOf.eissn
1664-3224