Expression of activation markers in circulating basophils and the relationship to allergen-induced bronchoconstriction in subjects with mild allergic asthma

Salter, Brittany; Nusca, Graeme; Tworek, Damian; Oliveria, John Paul; Smith, Steven G; Watson, Rick; Scime, Tara; Obminski, C; Sehmi, Roma; Gauvreau, Gail M.

doi:10.1016/j.jaci.2015.08.024

Cited by 11 publications

(10 citation statements)

References 7 publications

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“…Certainly, our findings do not exclude a role for TSLP (or any other EC cytokine) in activating human basophils, but every attempt thus far to test this hypothesis have proved negative. In this respect, it is important to note that Salter, et al recently provided evidence of TSLP activating human basophils for mediator release and cytokine production (12). This group investigated allergic asthmatics whose basophils were somewhat hyper-responsive, spontaneously releasing ~40% of total histamine in buffer alone.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, several studies support the existence of a so-called “basophil-TSLP axis” whereby the latter plays an important role in conditioning basophils for IL-4 production (10, 11). While evidence for this axis in humans has been less forthcoming, one group has recently reported on TSLP’s capacity to activate basophils from asthmatic subjects –a response dependent on IL-3 (12). These authors additionally report that other EC-derived cytokines (IL-25 & IL-33) activate basophils from asthmatics, particularly post allergen challenge (13).…”

Section: Introductionmentioning

confidence: 99%

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Activation of Human Basophils by A549 Lung Epithelial Cells Reveals a Novel IgE-Dependent Response Independent of Allergen

Schroeder

Bieneman

2017

The Journal of Immunology

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Evidence for epithelial cell (EC)-derived cytokines (e.g. TSLP) activating human basophils remains controversial. We therefore hypothesize that ECs can directly activate basophils via cell-to-cell interaction. Basophils in medium alone or with IL-3±anti-IgE, were co-incubated with TSLP, IL-33, or IL-25. Analogous experiments co-cultured basophils (1–72h) directly with EC lines. Supernatants were tested for mediators and cytokines. Antibodies targeting receptors were tested for neutralizing effects. Lactic acid (pH 3.9) treatment combined with passive sensitization tested the role of IgE. Overall, IL-33 augmented IL-13 secretion from basophils co-treated with IL-3, with minimal effects on histamine and IL-4. Conversely, basophils (but not mast cells) released histamine and marked levels of IL-4/IL-13 (10-fold) when co-cultured with A549 EC and IL-3, without exogenous allergen or IgE cross-linking stimuli. The inability to detect IL-33/TSLP, or to neutralize their activity, suggested a unique mode of basophil activation by A549 EC. Half-maximal rates for histamine (4h) and IL-4 (5h) secretion were slower than observed with standard IgE-dependent activation. Immunoglobulin stripping combined with passive sensitization±omalizumab showed a dependency for basophil-bound IgE, substantiated by requirement for cell-to-cell contact, aggregation, and FcεRI-dependent signaling. A yet unidentified IgE-binding lectin associated with A549 EC is implicated after discovering that n-acetyllactosamine suppressed basophil activation in co-cultures. These findings point to a lectin-dependent activation of basophil requiring IgE but independent of allergen or secreted cytokine. Pending further investigation, we predict this unique mode of activation is linked to inflammatory conditions whereby IgE-dependent activation of basophils occurs despite absence of any known allergen.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Activation of Human Basophils by A549 Lung Epithelial Cells Reveals a Novel IgE-Dependent Response Independent of Allergen

Schroeder

Bieneman

2017

The Journal of Immunology

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“…Typically, basophils are immunophenotypically defined by expression of the IL-3 receptor (IL-3R or CD123), lack of HLA-DR, constitutive expression of FcεRI, and more recently reported by expression of the activation marker, CD203c (Salter et al, 2016a(Salter et al, , 2016b. Human and mouse studies additionally exclude other cell subsets by specifying CD49b + , CD69 + , Thy-1.2 + , CD117 À , CD19 À , CD11c +/À , CD3 À , B220 À , NK1.1 À (i.e.…”

Section: Introductionmentioning

confidence: 99%

Mass Cytometry Phenotyping of Human Granulocytes Reveals Novel Basophil Functional Heterogeneity

et al. 2020

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Summary Basophils, the rarest granulocyte, play critical roles in parasite- and allergen-induced inflammation. We applied mass cytometry (CyTOF) to simultaneously asses 44 proteins to phenotype and functionally characterize neutrophils, eosinophils, and basophils from 19 healthy donors. There was minimal heterogeneity seen in eosinophils and neutrophils, but data-driven analyses revealed four unique subpopulations within phenotypically basophilic granulocytes (PBG; CD45 + HLA-DR − CD123 + ). Through CyTOF and fluorescence-activated cell sorting (FACS), we classified these four PBG subpopulations as (I) CD16 low FcεRI high CD244 high (88.5 ± 1.2%), (II) CD16 high FcεRI high CD244 high (9.1 ± 0.4%), (III) CD16 low FcεRI low CD244 low (2.3 ± 1.3), and (IV) CD16 high FcεRI low CD244 low (0.4 ± 0.1%). Prospective isolation confirmed basophilic-morphology of PBG I–III, but neutrophilic-morphology of PBG IV. Functional interrogation via IgE-crosslinking or IL-3 stimulation demonstrated that PBG I–II had significant increases in CD203c expression, whereas PBG III–IV remained unchanged compared with media-alone conditions. Thus, PBG III–IV could serve roles in non-IgE-mediated immunity. Our findings offer new perspectives in human basophil heterogeneity and the varying functional potential of these new subsets in health and disease.

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“…Previous studies examined the changes in expression of plasma proteins on circulating basophils during asthma exacerbation or after inhalation allergen challenge . Both scenarios are associated with increased CD203c expression on circulating basophils, but no differences were demonstrated for CD63.…”

Section: The Role Of Basophils In Asthmamentioning

confidence: 99%

Important and specific role for basophils in acute allergic reactions

Korošec

Gibbs

Rijavec

et al. 2018

Clin Experimental Allergy

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SummaryIgE‐mediated allergic reactions involve the activation of effector cells, predominantly through the high‐affinity IgE receptor (FcεRI) on mast cells and basophils. Although the mast cell is considered the major effector cell during acute allergic reactions, more recent studies indicate a potentially important and specific role for basophils and their migration which occurs rapidly upon allergen challenge in humans undergoing anaphylaxis. We review the evidence for a role of basophils in contributing to clinical symptoms of anaphylaxis and discuss the possibility that basophil trafficking during anaphylaxis might be a pathogenic (to target organs) or protective (preventing degranulation in circulation) response. Finally, we examine the potential role of basophils in asthma exacerbations. Understanding the factors that regulate basophil trafficking and activation might lead to new diagnostic and therapeutic strategies in anaphylaxis and asthma.

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Expression of activation markers in circulating basophils and the relationship to allergen-induced bronchoconstriction in subjects with mild allergic asthma

Cited by 11 publications

References 7 publications

Activation of Human Basophils by A549 Lung Epithelial Cells Reveals a Novel IgE-Dependent Response Independent of Allergen

Activation of Human Basophils by A549 Lung Epithelial Cells Reveals a Novel IgE-Dependent Response Independent of Allergen

Mass Cytometry Phenotyping of Human Granulocytes Reveals Novel Basophil Functional Heterogeneity

Important and specific role for basophils in acute allergic reactions

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