IgE antibodies increase honeybee venom responsiveness and detoxification efficiency of mast cells

Autor: Stephen J. Galli, Martin L. Watzenboeck, Nicolas Gaudenzio, Thomas Marichal, Sylvia Knapp, Philipp Starkl, Frédéric Fontaine, Mindy Tsai, Riccardo Sibilano, Laurent L. Reber, André C. Mueller
Přispěvatelé: Research Center for Molecular Medicine of the Austrian Academy of Sciences [Vienna, Austria] (CeMM ), Austrian Academy of Sciences (OeAW), Medizinische Universität Wien = Medical University of Vienna, Department of Pathology [Stanford], Stanford Medicine, Stanford University-Stanford University, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), GIGA [Université Liège], Université de Liège, Sean N. Parker Center for Allergy and Asthma Research [Stanford], Department of Microbiology and Immunology [Stanford], ANR-18-CE18-0023,AllergyVACS,Développement d'un vaccin thérapeutique pour les maladies allergiques(2018), European Project: 802041, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pistre, Karine, APPEL À PROJETS GÉNÉRIQUE 2018 - Développement d'un vaccin thérapeutique pour les maladies allergiques - - AllergyVACS2018 - ANR-18-CE18-0023 - AAPG2018 - VALID, ERC-2018-STG - 802041 - INCOMING
Rok vydání: 2021
Předmět:
0301 basic medicine
[SDV]Life Sciences [q-bio]
Immunoglobulin E
Cell Degranulation
Mice
MESH: Bee Venoms
0302 clinical medicine
MESH: Heparin / metabolism
Immunology and Allergy
MESH: Animals
Mast Cells
Cytotoxicity
Sensitization
biology
honeybee venom
Chemistry
MESH: Immunoglobulin E
Degranulation
MESH: Mast Cells
MESH: Allergens / metabolism
3. Good health
[SDV] Life Sciences [q-bio]
Bee Venoms
medicine.anatomical_structure
host defense
MESH: Cell Degranulation
[SDV.IMM]Life Sciences [q-bio]/Immunology
IgE
Antibody
MESH: Peptide Hydrolases / metabolism
Proteases
[SDV.IMM] Life Sciences [q-bio]/Immunology
Immunology
toxin hypothesis
03 medical and health sciences
Immune system
In vivo
medicine
Animals
Humans
MESH: Mice
MESH: Humans
Heparin
Allergens
030104 developmental biology
030228 respiratory system
biology.protein
Peptide Hydrolases
Zdroj: Allergy
Allergy, 2022, 77 (2), pp.499-512. ⟨10.1111/all.14852⟩
ISSN: 1398-9995
0105-4538
DOI: 10.1111/all.14852⟩
Popis: International audience; Background: In contrast to their clearly defined roles in allergic diseases, the physiologic functions of Immunoglobulin E antibodies (IgEs) and mast cells (MCs) remain enigmatic. Recent research supports the toxin hypothesis, showing that MCs and IgE-related type 2 immune responses can enhance host defense against certain noxious substances, including honeybee venom (BV). However, the mechanisms by which MCs can interfere with BV toxicity are unknown. In this study, we assessed the role of IgE and certain MC products in MC-mediated BV detoxification.Methods: We applied in vitro and in vivo fluorescence microscopyimaging, and flow cytometry, fibroblast-based toxicity assays and mass spectrometry to investigate IgE-mediated detoxification of BV cytotoxicity by mouse and human MCs in vitro. Pharmacologic strategies to interfere with MC-derived heparin and proteases helped to define the importance of specific detoxification mechanisms.Results: Venom-specific IgE increased the degranulation and cytokine responses of MCs to BV in vitro. Passive serum sensitization enhanced MC degranulation in vivo. IgE-activated mouse or human MCs exhibited enhanced potential for detoxifying BV by both proteolytic degradation and heparin-related interference with toxicity. Mediators released by IgE-activated human MCs efficiently degraded multiple BV toxins.Conclusions: Our results both reveal that IgE sensitization enhances the MC's ability to detoxify BV and also assign efficient toxin-neutralizing activity to MC-derived heparin and proteases. Our study thus highlights the potential importance of IgE, MCs, and particular MC products in defense against BV.
Databáze: OpenAIRE
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