IgE expression pattern in lung: Relation to systemic IgE and asthma phenotypes

Balzar, Silvana; Strand, Matthew; Rhodes, Diane; Wenzel, Sally E.

doi:10.1016/j.jaci.2006.12.642

Cited by 61 publications

(57 citation statements)

References 33 publications

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“…Although general quantitative and phenotype changes in total MCs have been reported with conditions such as asthma and COPD, functional characteristics of IHC-identified MC TC remain poorly understood (3)(4)(5)(6)(7)(8)17). In vitro studies show that the two MC phenotypes functionally differ.…”

Section: What This Study Adds To the Fieldmentioning

confidence: 99%

“…Although a plethora of studies suggest alterations in mast cells (MCs) may underlie its pathogenesis, their specific role is unclear (3)(4)(5)(6)(7)(8).…”

mentioning

confidence: 99%

“…Normally, MC T predominate in the lung, whereas MC TC represent less than 20% of lung MCs. The distribution of MC phenotypes within a particular organ/tissue varies as well (3)(4)(5)(6)(7)(8).…”

mentioning

confidence: 99%

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Mast Cell Phenotype, Location, and Activation in Severe Asthma

Balzar¹,

Fajt²,

Comhair³

et al. 2011

Am J Respir Crit Care Med

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271

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Rationale: Severe asthma (SA) remains poorly understood. Mast cells (MC) are implicated in asthma pathogenesis, but it remains unknown how their phenotype, location, and activation relate to asthma severity. Objectives: To compare MC-related markers measured in bronchoscopically obtained samples with clinically relevant parameters between normal subjects and subjects with asthma to clarify their pathobiologic importance. Methods: Endobronchial biopsies, epithelial brushings, and bronchoalveolar lavage were obtained from subjects with asthma and normal subjects from the Severe Asthma Research Program (N 5 199). Tryptase, chymase, and carboxypeptidase A (CPA)3 were used to identify total MC (MC Tot ) and the MC TC subset (MCs positive for both tryptase and chymase) using immunostaining and quantitative real-time polymerase chain reaction. Lavage was analyzed for tryptase and prostaglandin D2 (PGD2) by ELISA. Measurements and Main Results: Submucosal MC Tot (tryptase-positive by immunostaining) numbers were highest in ''mild asthma/no inhaled corticosteroid (ICS) therapy'' subjects and decreased with greater asthma severity (P 5 0.002). In contrast, MC TC (chymasepositive by immunostaining) were the predominant (MC TC /MC Tot . 50%) MC phenotype in SA (overall P 5 0.005). Epithelial MC Tot were also highest in mild asthma/no ICS, but were not lower in SA. Instead, they persisted and were predominantly MC TC . Epithelial CPA3 and tryptase mRNA supported the immunostaining data (overall P 5 0.008 and P 5 0.02, respectively). Lavage PGD2 was higher in SA than in other steroid-treated groups (overall P 5 0.02), whereas tryptase did not differentiate the groups. In statistical models, PGD2 and MC TC /MC Tot predicted SA. Conclusions: Severe asthma is associated with a predominance of MC TC in the airway submucosa and epithelium. Activation of those MC TC may contribute to the increases in PGD2 levels. The data suggest an altered and active MC population contributes to SA pathology.

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Section: What This Study Adds To the Fieldmentioning

confidence: 99%

“…Although a plethora of studies suggest alterations in mast cells (MCs) may underlie its pathogenesis, their specific role is unclear (3)(4)(5)(6)(7)(8).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Mast Cell Phenotype, Location, and Activation in Severe Asthma

Balzar¹,

Fajt²,

Comhair³

et al. 2011

Am J Respir Crit Care Med

Self Cite

271

242

View full text Add to dashboard Cite

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“…Previous studies have shown that IgE is frequently present in the mucosal secretions of airway tract, and its level can be enhanced in human patients with asthma (8,11). Transferring of the intact allergen molecule across the airway epithelial barrier may be an important event in priming a host for an allergen, and subsequent exposure of same allergen leads to the development of allergic inflammation.…”

Section: Cd23 Transcytoses Ige-derived Ic Across Polarized Calu-3 Cellsmentioning

confidence: 99%

“…Clinical studies have found a close association between asthma and serum IgE levels, and the amount of allergen-specific IgE can be dramatically increased in sensitized or atopy patients (7,8). Allergen-specific IgE is located in the human airway, such as in nasal mucosa from allergic patients who suffer allergic rhinitis in sinonasal tissue, nasal polyposis, and allergic fungal rhinosinusitis (9)(10)(11)(12). This observation is further supported by the fact that B cells from the nasal mucosa of allergic individuals locally synthesize IgE (13,14).…”

mentioning

confidence: 99%

CD23-Dependent Transcytosis of IgE and Immune Complex across the Polarized Human Respiratory Epithelial Cells

Palaniyandi

Tomei

et al. 2011

The Journal of Immunology

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IgE-mediated allergic inflammation occurs when allergens cross-link IgE on the surface of immune cells, thereby triggering the release of inflammatory mediators as well as enhancing Ag presentations. IgE is frequently present in airway secretions, and its level can be enhanced in human patients with allergic rhinitis and bronchial asthma. However, it remains completely unknown how IgE appears in the airway secretions. In this study, we show that CD23 (FcεRII) is constitutively expressed in established or primary human airway epithelial cells, and its expression is significantly upregulated when airway epithelial cells were subjected to IL-4 stimulation. In a transcytosis assay, human IgE or IgE-derived immune complex (IC) was transported across a polarized Calu-3 monolayer. Exposure of the Calu-3 monolayer to IL-4 stimulation also enhanced the transcytosis of either human IgE or the IC. A CD23-specific Ab or soluble CD23 significantly reduced the efficiency of IgE or IC transcytosis, suggesting a specific receptor-mediated transport by CD23. Transcytosis of both IgE and the IC was further verified in primary human airway epithelial cell monolayers. Furthermore, the transcytosed Ag–IgE complexes were competent in inducing degranulation of the cultured human mast cells. Because airway epithelial cells are the first cell layer to come into contact with inhaled allergens, our study implies CD23-mediated IgE transcytosis in human airway epithelial cells may play a critical role in initiating and contributing to the perpetuation of airway allergic inflammation.

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