Abstract
Background and AimsSpecific hyper-responsiveness towards an allergen and non-specific airway hyperreactivity both impair quality of life in patients with respiratory allergic diseases. We aimed to investigate cellular responses following specific and non-specific airway challenges locally and systemically in i) sensitized BALB/c mice challenged with grass pollen allergen Phl p 5, and in ii) grass pollen sensitized allergic rhinitis subjects undergoing specific airway challenge in the Vienna Challenge Chamber (VCC).Methods and ResultsBALB/c mice (n = 20) were intraperitoneally immunized with grass pollen allergen Phl p 5 and afterwards aerosol challenged with either the specific allergen Phl p 5 (n = 10) or the non-specific antigen ovalbumin (OVA) (n = 10). A protocol for inducing allergic asthma as well as allergic rhinitis, according to the united airway concept, was used. Both groups of exposed mice showed significantly reduced physical activity after airway challenge. Specific airway challenge further resulted in goblet cell hyperplasia, enhanced mucous secretion, intrapulmonary leukocyte infiltration and lymphoid follicle formation, associated with significant expression of IL-4, IL-5 and IL-13 in splenocytes and also partially in lung tissue. Concerning circulating blood cell dynamics, we observed a significant drop of erythrocyte counts, hemoglobin and hematocrit levels in both mouse groups, challenged with allergen or OVA. A significant decrease in circulating erythrocytes and hematocrit levels after airway challenges with grass pollen allergen was also found in grass pollen sensitized human rhinitis subjects (n = 42) at the VCC. The effects on peripheral leukocyte counts in mice and humans however were opposed, possibly due to the different primary inflammation sites.ConclusionOur data revealed that, besides significant leukocyte dynamics, particularly erythrocytes are involved in acute hypersensitivity reactions to respiratory allergens. A rapid recruitment of erythrocytes to the lungs to compensate for hypoxia is a possible explanation for these findings.
Highlights
Our data revealed that, besides significant leukocyte dynamics, erythrocytes are involved in acute hypersensitivity reactions to respiratory allergens
A rapid recruitment of erythrocytes to the lungs to compensate for hypoxia is a possible explanation for these findings
[21] IL-5 is primarily engaged in the recruitment of eosinophils, which negatively correlate with nasal airflow in asthma and rhinitis patients
Summary
The prevalence of allergy mediated medical conditions is increasing worldwide and currently affecting approximately a fifth of the world population. [1] Especially allergic airway diseases are associated with significant quality of life limitations in affected patients. [2] less limiting than bronchial asthma, allergic rhinitis has been described as a global health concern causing major illness and disability worldwide. [3] Allergic rhinitis and allergic asthma are often found in the same patients and considered manifestations of the same inflammatory disease emphasized in different parts of the airways [2,3].Allergic asthma is defined as a chronic inflammatory disorder of the lower airways and is characterized by airway inflammation, persistent airway hyperresponsiveness (AHR) and intermittent acute, reversible airways obstruction. [4] Typically, the IgEmediated, immediate obstruction is followed by a late phase reaction triggered by the release of inflammatory mediators like leukotrienes and cytokines (i.e. IL-4) from cells recruited to the lungs. [1] Especially allergic airway diseases are associated with significant quality of life limitations in affected patients. [4] Typically, the IgEmediated, immediate obstruction is followed by a late phase reaction triggered by the release of inflammatory mediators like leukotrienes and cytokines (i.e. IL-4) from cells recruited to the lungs. This results in respiratory and, physical deficits of affected patients for a considerable time after an asthma attack. Specific hyper-responsiveness towards an allergen and non-specific airway hyperreactivity both impair quality of life in patients with respiratory allergic diseases. We aimed to investigate cellular responses following specific and non-specific airway challenges locally and systemically in i) sensitized BALB/c mice challenged with grass pollen allergen Phl p 5, and in ii) grass pollen sensitized allergic rhinitis subjects undergoing specific airway challenge in the Vienna Challenge Chamber (VCC)
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