IgE-dependent human basophil responses are inversely associated with the sarcoplasmic reticulum Ca2+-ATPase (SERCA)
Basophils crucially contribute to allergies and other Th2-driven diseases by rapidly releasing inflammatory and immunomodulatory mediators following high-affinity IgE-receptor crosslinking. Although these basophil-mediated responses depend on sensitization with antigen-specific IgE, this does not ne...
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| Format: | Article |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1052290/full |
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| author | Anette T. Hansen Selnø Vadim V. Sumbayev Bernhard F. Gibbs Bernhard F. Gibbs |
| author_facet | Anette T. Hansen Selnø Vadim V. Sumbayev Bernhard F. Gibbs Bernhard F. Gibbs |
| author_sort | Anette T. Hansen Selnø |
| collection | DOAJ |
| description | Basophils crucially contribute to allergies and other Th2-driven diseases by rapidly releasing inflammatory and immunomodulatory mediators following high-affinity IgE-receptor crosslinking. Although these basophil-mediated responses depend on sensitization with antigen-specific IgE, this does not necessarily predict clinical symptom severity. It is thought that the balance of early stimulatory (e.g. SYK) and inhibitory (e.g. SHIP-1) intracellular signals are associated with basophil responsiveness, which is also critically dependent on calcium mobilization. Previous studies suggest that the sarcoplasmic reticulum Ca2+-ATPase (SERCA2), which regulates cytosolic calcium levels, may be inversely associated with airway smooth muscle reactivity in asthma. Since basophils are implicated in asthma severity, our aims were to address whether SERCA2 is implicated in human basophil responses, especially following IgE-mediated activation. Human basophils were obtained from buffy coats, following research ethics approval, and further purified by immunomagnetic cell sorting. Expressions of SERCA2, and other isoforms, were determined by Western blotting in parallel to measuring IgE-dependent histamine releases from the same donors. The effects of a SERCA-activator and inhibitor were also assessed on their abilities to modulate basophil histamine release. We observed an inverse correlation between basophil responsiveness to IgE-dependent stimulation and SERCA2 expression. Thapsigargin, a highly-specific SERCA inhibitor, stimulated basophil histamine release and potentiated IgE-dependent secretion of the amine. Conversely, disulfiram, a SERCA activator, inhibited IgE-dependent basophil activation. The results obtained from this exploratory study indicate that SERCA2 may be an additional regulator of basophil reactivity alongside early excitatory or inhibitory signal transduction pathways. |
| first_indexed | 2024-04-11T00:57:59Z |
| format | Article |
| id | doaj.art-b43da17b1e10421fa90919f92a8c7df8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T00:57:59Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b43da17b1e10421fa90919f92a8c7df82023-01-04T21:22:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011310.3389/fimmu.2022.10522901052290IgE-dependent human basophil responses are inversely associated with the sarcoplasmic reticulum Ca2+-ATPase (SERCA)Anette T. Hansen Selnø0Vadim V. Sumbayev1Bernhard F. Gibbs2Bernhard F. Gibbs3School of Pharmacy, University of Kent, Chatham Maritime, United KingdomSchool of Pharmacy, University of Kent, Chatham Maritime, United KingdomSchool of Pharmacy, University of Kent, Chatham Maritime, United KingdomDepartment of Human Medicine, University of Oldenburg, Oldenburg, GermanyBasophils crucially contribute to allergies and other Th2-driven diseases by rapidly releasing inflammatory and immunomodulatory mediators following high-affinity IgE-receptor crosslinking. Although these basophil-mediated responses depend on sensitization with antigen-specific IgE, this does not necessarily predict clinical symptom severity. It is thought that the balance of early stimulatory (e.g. SYK) and inhibitory (e.g. SHIP-1) intracellular signals are associated with basophil responsiveness, which is also critically dependent on calcium mobilization. Previous studies suggest that the sarcoplasmic reticulum Ca2+-ATPase (SERCA2), which regulates cytosolic calcium levels, may be inversely associated with airway smooth muscle reactivity in asthma. Since basophils are implicated in asthma severity, our aims were to address whether SERCA2 is implicated in human basophil responses, especially following IgE-mediated activation. Human basophils were obtained from buffy coats, following research ethics approval, and further purified by immunomagnetic cell sorting. Expressions of SERCA2, and other isoforms, were determined by Western blotting in parallel to measuring IgE-dependent histamine releases from the same donors. The effects of a SERCA-activator and inhibitor were also assessed on their abilities to modulate basophil histamine release. We observed an inverse correlation between basophil responsiveness to IgE-dependent stimulation and SERCA2 expression. Thapsigargin, a highly-specific SERCA inhibitor, stimulated basophil histamine release and potentiated IgE-dependent secretion of the amine. Conversely, disulfiram, a SERCA activator, inhibited IgE-dependent basophil activation. The results obtained from this exploratory study indicate that SERCA2 may be an additional regulator of basophil reactivity alongside early excitatory or inhibitory signal transduction pathways.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1052290/fullbasophilsSERCAIgE receptorhistamineinhibitory signaling |
| spellingShingle | Anette T. Hansen Selnø Vadim V. Sumbayev Bernhard F. Gibbs Bernhard F. Gibbs IgE-dependent human basophil responses are inversely associated with the sarcoplasmic reticulum Ca2+-ATPase (SERCA) Frontiers in Immunology basophils SERCA IgE receptor histamine inhibitory signaling |
| title | IgE-dependent human basophil responses are inversely associated with the sarcoplasmic reticulum Ca2+-ATPase (SERCA) |
| title_full | IgE-dependent human basophil responses are inversely associated with the sarcoplasmic reticulum Ca2+-ATPase (SERCA) |
| title_fullStr | IgE-dependent human basophil responses are inversely associated with the sarcoplasmic reticulum Ca2+-ATPase (SERCA) |
| title_full_unstemmed | IgE-dependent human basophil responses are inversely associated with the sarcoplasmic reticulum Ca2+-ATPase (SERCA) |
| title_short | IgE-dependent human basophil responses are inversely associated with the sarcoplasmic reticulum Ca2+-ATPase (SERCA) |
| title_sort | ige dependent human basophil responses are inversely associated with the sarcoplasmic reticulum ca2 atpase serca |
| topic | basophils SERCA IgE receptor histamine inhibitory signaling |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1052290/full |
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