Basophils and allergic inflammation

Siracusa, Mark C.; Kim, Brian; Spergel, Jonathan M.; Artis, David

doi:10.1016/j.jaci.2013.07.046

Cited by 258 publications

(230 citation statements)

References 147 publications

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“…Basophils play multiple roles in type 2 immunity and allergy (11)(12)(13). Basophils also have been shown to be activated by various cysteine proteases, including papain, bromelain (9), and Der p 1, an allergen produced by the house dust mite Dermatophagoides pteronyssinus (14).…”

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confidence: 99%

Signaling pathways activated by a protease allergen in basophils

Rosenstein

Bezbradica

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Allergic diseases represent a significant burden in industrialized countries, but why and how the immune system responds to allergens remain largely unknown. Because many clinically significant allergens have proteolytic activity, and many helminths express proteases that are necessary for their life cycles, host mechanisms likely have evolved to detect the proteolytic activity of helminth proteases, which may be incidentally activated by protease allergens. A cysteine protease, papain, is a prototypic protease allergen that can directly activate basophils and mast cells, leading to the production of cytokines, including IL-4, characteristic of the type 2 immune response. The mechanism of papain's immunogenic activity remains unknown. Here we have characterized the cellular response activated by papain in basophils. We find that papain-induced IL-4 production requires calcium flux and activation of PI3K and nuclear factor of activated T cells. Interestingly, papain-induced IL-4 production was dependent on the immunoreceptor tyrosine-based activation motif (ITAM) adaptor protein Fc receptor γ-chain, even though the canonical ITAM signaling was not activated by papain. Collectively, these data characterize the downstream signaling pathway activated by a protease allergen in basophils.allergen | basophil | signaling

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mentioning

confidence: 99%

Signaling pathways activated by a protease allergen in basophils

Rosenstein

Bezbradica

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…When allergens are presented to T and B lymphocytes, those secrete allergen-specific IgE antibodies that circulate in the peripheral blood stream, and attach to mast cells and basophils on the nasal mucosa [18,19]. Subsequent exposure to allergens activates these cells which instantly produce the classical inflammatory mediators of allergic reactions, including histamines [20].…”

Section: Discussionmentioning

confidence: 99%

A New Class of Polymeric Anti-Allergen Nasal Barrier Film Solution for the Treatment of Allergic Rhinitis

Shrivastava¹,

Schütte²,

Malik³

et al. 2017

J Allergy Ther

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Objective: Allergic rhinitis (AR) is oversensitivity of nasal mucosa to allergen exposure leading to IgE-mediated nasal mucosal inflammation and cellular destruction. Applying any chemical drug over the nasal mucosa may provide symptomatic relief but at the same time the presence of chemicals, such as cortisones and antihistaminic, hampers mucosa repair and, in consequence, cellular defense functions. Therefore, cleaning, avoiding allergen exposure, and protecting nasal mucosa from contact with allergens with a cell-friendly mechanical device, could be an effective remedy to treat allergic rhinitis. Methods:A double blind, randomized, placebo controlled, multicenter clinical trial was conducted in patients suffering from severe AR. 15 patients were treated with saline as comparator product (CP) versus 31 treated with the test product (TP). The test product contained a natural gum-glycerol solution (VB-Gy) which was rendered filmogen using inert natural polymers (Allercyanidin-H) and termed as VB-Gy-Allercyanidin-H formula. The products (15 ml sprays) were applied topically over the nasal mucosa, 3-4 times a day over a period of 3 weeks. Total, reflective and instantaneous nasal symptom scores for rhinorrhea, nasal discharge, sneezing, and itching, as well as ocular scores (itching, tearing, redness) and rescue medicine use scores were evaluated daily during weeks -1 to +3 employing a 0 (no symptoms) to 3 (severe symptoms) scoring scale. Rhino-conjunctivitis quality of life (RQLQ) questionnaires were completed at the start and at the end of the study. Saline solution (CP) was used identically to the TP. Mean weekly results in CP and TP groups were compared with the scores at the start of treatment (baseline) and between the two groups.Results: CP was found to reduce only slightly the symptomatic manifestation of allergic rhinitis. The mean reduction compared to baseline at the end of weeks 1, 2, and 3 was respectively 11.7%, 13.6% and 15.1% for total nasal symptom scores (rTNSS); 9.9%, 14.5%, and 15.8% for total ocular symptom scores (rTOSS); and 4.97%, 8.45%, and 10.94% for pre-dose instantaneous total ocular symptom scores (am-iTOSS, p: Not Significant: NS). During the same period, compared to CP scores, the reduction in TP group was higher by 37.7%, 58.4%, and 73.5% for rTNSS; 38.3%, 54.6%, and 64.1% for rTOSS and 29.84%, 48.91%, and 59.77% for am-iTOSS (p<0.05 for all parameters vs. CP at the same time points). The rhinoconjunctivitis quality of life questionnaire (RQLQ), measured using standard established questionnaire, was improved by 50.28% in TP group compared to 22.85% in CP group. During the study period, at least one rescue medicine was used by 80% patients in CP group compared to only 29% in TP group. Both products were well tolerated and induced no undesired effects. Conclusion:In the absence of any cell-friendly, safe, and multi-target treatment for allergic rhinitis, using a mechanically acting, filmogen barrier solution capable of blocking new allergen contact and minimizing the concentra...

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“…Basophils, which are cells derived from basophil/mast cell precursor cells in the bone marrow, comprise less than 1% of the blood leukocytes and share some characteristics with mast cells phenotypically and functionally, such that they both can act as important effector cells in allergic airway inflammation (5,6). Numerous studies have demonstrated that basophils not only play crucial roles in the effector phase, but also critically participate in the initiation of Th2-centered immune responses (7)(8)(9)(10)(11).…”

Section: Asthma Is Characterized By Increased Airway Submucosal Infilmentioning

confidence: 99%

Basophil-associated OX40 Ligand Participates in the Initiation of Th2 Responses during Airway Inflammation

Lin

Zhang

et al. 2015

Journal of Biological Chemistry

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Background: Basophils play a great role in the induction of Th2 cell responses in different disease contexts. Results: Basophils highly expressed OX40 ligand (OX40L) after activation. Adoptive transfer of activated basophils triggered a robust Th2 response and airway inflammation. Conclusion: Basophils primed Th2 responses via OX40-OX40L interaction in asthma. Significance: OX40L on basophils may be a novel therapeutic target in asthma.

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Basophils and allergic inflammation

Cited by 258 publications

References 147 publications

Signaling pathways activated by a protease allergen in basophils

Signaling pathways activated by a protease allergen in basophils

A New Class of Polymeric Anti-Allergen Nasal Barrier Film Solution for the Treatment of Allergic Rhinitis

Basophil-associated OX40 Ligand Participates in the Initiation of Th2 Responses during Airway Inflammation

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