Histamine-Releasing Factor Is a Novel Alarmin Induced by House Dust Mite Allergen, Cytokines, and Cell Death

Copyright © 2022 by The American Association of Immunologists, Inc..

Histamine-releasing factor (HRF) is a multifunctional protein with fundamental intracellular functions controlling cell survival and proliferation. HRF is also secreted during allergic reactions and promotes IgE-mediated activation of mast cells and basophils. In this study, we investigated HRF secretion and its relevance to airway inflammation. HRF monomers were constitutively secreted from BEAS-2B human bronchial epithelial cells (HBECs) and converted to oligomers over the course of culture. Stimulation with house dust mite (HDM) extract increased HRF secretion substantially. Several cytokines involved in asthma pathogenesis showed moderate effects on HRF secretion but dramatically enhanced HDM-induced HRF secretion. HDM-induced HRF secretion from BEAS-2B cells and normal HBECs proceeded via TLR2. Consistent with this, multiple TLR2 ligands, including Der p 2, Der p 5, Der p 13, and Der p 21, induced HRF secretion. Der p 10 (tropomyosin) also promoted HRF secretion. Cell death or incubation with adenosine and ATP, compounds released upon cell death, also enhanced HRF secretion. Furthermore, intranasal administration of recombinant HRF elicited robust airway inflammation in HDM-sensitized mice in an FcεRI-dependent manner. Therefore, we conclude that HRF is a novel alarmin that promotes allergic airway inflammation.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:209

Enthalten in:

Journal of immunology (Baltimore, Md. : 1950) - 209(2022), 10 vom: 15. Nov., Seite 1851-1859

Sprache:

Englisch

Beteiligte Personen:

Kasakura, Kazumi [VerfasserIn]
Kawakami, Yu [VerfasserIn]
Jacquet, Alain [VerfasserIn]
Kawakami, Toshiaki [VerfasserIn]

Links:

Volltext

Themen:

820484N8I3
9001-32-5
Alarmins
Allergens
Antigens, Dermatophagoides
Cytokines
Fibrinogen
Histamine
Immunologic Factors
Journal Article
Research Support, N.I.H., Extramural
Toll-Like Receptor 2
Tumor Protein, Translationally-Controlled 1

Anmerkungen:

Date Completed 29.11.2022

Date Revised 16.11.2023

published: Print

Citation Status MEDLINE

doi:

10.4049/jimmunol.2200276

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM349398976