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Targeted inhibition of allergen‐induced histamine production by neutrophils
Author(s) -
Chacón Pedro,
VegaRioja Antonio,
Doukkali Bouchra,
del Valle Rodríguez Alberto,
Bellido Virginia,
Puente Yolanda,
Alcañiz Lorena,
Rodríguez David,
Palacios Ricardo,
CornejoGarcía José Antonio,
Monteseirín Javier,
RivasPérez David
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202001912r
Subject(s) - histamine , histamine h4 receptor , histidine decarboxylase , histamine receptor , allergen , histamine n methyltransferase , histamine h2 receptor , pharmacology , immunology , allergic response , chemistry , histamine h1 receptor , diamine oxidase , immunoglobulin e , receptor , allergy , medicine , enzyme , biochemistry , histidine , antibody , antagonist
Abstract Histamine is a critical inflammatory mediator in allergic diseases. We showed in a previous work that neutrophils from allergic patients produce histamine in response to allergens to which the patients were sensitized. Here, we investigate the molecular mechanisms involved in this process using peripheral blood neutrophils. We challenged these cells in vitro with allergens and analyzed histamine release in the culture supernatants. We also explored the effect of common therapeutic drugs that ameliorate allergic symptoms, as well as allergen‐specific immunotherapy. Additionally, we examined the expression of histidine decarboxylase and diamine oxidase, critical enzymes in the metabolism of histamine, under allergen challenge. We show that allergen‐induced histamine release is dependent on the activation of the phosphoinositide 3‐kinase, mitogen‐activated protein kinase p38, and extracellular signal‐regulated kinase 1/2 signaling pathways. We also found a contribution of the phosphatase calcineurin to lesser extent. Anti‐histamines, glucocorticoids, anti‐M3‐muscarinic receptor antagonists, and mainly β 2 ‐receptor agonists abolished the allergen‐dependent histamine release. Interestingly, allergen‐specific immunotherapy canceled the histamine release through the downregulation of histidine decarboxylase expression. Our observations describe novel molecular mechanisms involved in the allergen‐dependent histamine release by human neutrophils and provide new targets to inhibit histamine production.