ArticleThe Journal of allergy and clinical immunology2015
Estrogen increases the severity of anaphylaxis in female mice through enhanced endothelial nitric oxide synthase expression and nitric oxide production.
Article in The Journal of allergy and clinical immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Hypersensitivity to Gadolinium-Based Contrast Media.Frontiers in allergy · 2022Pooled it
- Sexual Dimorphism in Allergic and Mast Cell-Associated Diseases.Clinical reviews in allergy & immunology · 2026Review
- Women hormones and hypersensitivity: allergic diseases in menopause.Frontiers in allergy · 2026Review
- IL-33 induces stronger responses in female mast cells and neutrophils: a role for the JNK pathway.Frontiers in immunology · 2026Article
- Natural History and Risk Factors of Hymenoptera Venom Allergy in Dogs.Animals : an open access journal from MDPI · 2024Article
- Anaphylaxis in a country where Asia and Europe meet: Evaluation according to World Allergy Organization (WAO) and European Academy of Allergy and Clinical Immunology (EAACI) diagnostic criteria.The World Allergy Organization journal · 2024Article
- Identifying patients at risk of anaphylaxis.The World Allergy Organization journal · 2024Review
- Intrinsic endothelial hyperresponsiveness to inflammatory mediators drives acute episodes in models of Clarkson disease.The Journal of clinical investigation · 2024Article
- Article
- Latin American anaphylaxis registry.The World Allergy Organization journal · 2023Article
- Article
- Effects of Biological Sex and Pregnancy on SARS-CoV-2 Pathogenesis and Vaccine Outcomes.Current topics in microbiology and immunology · 2023Article
- New Mechanistic Advances in FcεRI-Mast Cell-Mediated Allergic Signaling.Clinical reviews in allergy & immunology · 2022Review
- Sex Differences in Mast Cell-Associated Disorders: A Life Span Perspective.Cold Spring Harbor perspectives in biology · 2022Review
- Allergic Reactions to COVID-19 Vaccines: Risk Factors, Frequency, Mechanisms and Management.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2022Review
- Diamine oxidase knockout mice are not hypersensitive to orally or subcutaneously administered histamine.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Defining baseline variability of serum tryptase levels improves accuracy in identifying anaphylaxis.The Journal of allergy and clinical immunology · 2022Article
- Murine Q Fever Vaccination Model Reveals Sex Dimorphism in Early Phase Delayed-Type Hypersensitivity Responses.Frontiers in immunology · 2022Article
- Clinical relevance of inherited genetic differences in human tryptases: Hereditary alpha-tryptasemia and beyond.Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2021Review
- Potential mechanisms of anaphylaxis to COVID-19 mRNA vaccines.The Journal of allergy and clinical immunology · 2021Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundClinical observations suggest that anaphylaxis is more common in adult women compared with adult men, although the mechanistic basis for this sex bias is not well understood.
objectivesWe sought to document sex-dependent differences in a mouse model of anaphylaxis and explore the role of female sex hormones and the mechanisms responsible.
methodsPassive systemic anaphylaxis was induced in female and male mice by using histamine, as well as IgE or IgG receptor aggregation. Anaphylaxis was assessed by monitoring body temperature, release of mast cell mediators and/or hematocrit, and lung weight as a measure of vascular permeability. A combination of ovariectomy, estrogen receptor antagonism, and estrogen administration techniques were used to establish estrogen involvement.
resultsAnaphylactic responses were more pronounced in female than male mice. The enhanced severity of anaphylaxis in female mice was eliminated after pretreatment with an estrogen receptor antagonist or ovariectomy but restored after administration of estradiol in ovariectomized mice, demonstrating that the sex-specific differences are due to the female steroid estradiol. Estrogen did not affect mast cell responsiveness or anaphylaxis onset. Instead, it increased tissue expression of endothelial nitric oxide synthase (eNOS). Blockage of NOS activity with the inhibitor L-NG-nitroarginine methyl ester or genetic eNOS deficiency abolished the sex-related differences.
conclusionOur study defines a contribution of estrogen through its regulation of eNOS expression and nitric oxide production to vascular hyperpermeability and intensified anaphylactic responses in female mice, providing additional mechanistic insights into risk factors and possible implications for clinical management in the further exploration of human anaphylaxis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.