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PI3-Kinase Regulates Eosinophil and Neutrophil Degranulation in Patients with Allergic Rhinitis and Allergic Asthma Irrespective of Allergen Challenge Model

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Abstract

The PI3K pathway plays a major role in many vital cell processes. Our primary aim was to investigate signalling through PI3K for in vitro degranulation from allergen-primed eosinophils and neutrophils in allergic rhinitis and allergic asthma after seasonal and experimental allergen challenge. Nine patients with allergic rhinitis, eight with allergic asthma and four controls were studied during birch pollen season and after nasal and bronchial allergen challenge. Primed blood eosinophils and neutrophils were stimulated for in vitro degranulation with C3b-coated Sephadex particles, after prior incubation with Wortmannin, a PI3K inhibitor. The released amounts of eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and myeloperoxidase (MPO) were measured by radioimmunoassay. Wortmannin (10−6 to 10−9 M) inhibited ECP, EPO and MPO release in a dose-dependent manner in allergic rhinitis and allergic asthma in all three allergen challenge models. Inhibition of ECP release tended to be lower in the asthmatics in all allergen challenge models, statistically significant compared to the controls during season for 10−8 M Wortmannin (p = 0.01). A clear propensity towards less inhibition in the rhinitic patients was seen after nasal and bronchial challenge compared to seasonal exposure, significant for ECP (10−8 M Wortmannin; p = 0.034 and 0.002, respectively). Signalling through PI3K is clearly involved in ECP, EPO and MPO release in allergic rhinitis and allergic asthma irrespective of allergen challenge model. Allergic asthma demonstrated less inhibition of ECP release via PI3K during pollen season, indicating that other pathways play a greater role in eosinophil degranulation in allergic asthma than allergic rhinitis.

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Acknowledgement

The study was supported financially by the Swedish Association against Asthma and Allergy, the Swedish Heart and Lung Foundation and Bror Hjerpstedt’s Foundation. The nurses Signe Svedberg Brandt and Katarina Göthberg are acknowledged for the skilful technical assistance. We also acknowledge Dominic-Luc Webb, Hepatology and Gastroenterology Group, Dept of Medical Sciences, Uppsala University, for skilful linguistic review.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

Mary Kämpe, Marie Carlson and Gunnemar Stålenheim designed the study and were responsible, together with Christer Janson, for analysing and interpreting the results as well as critically revising the manuscript. Maria Lampinen was involved in drafting the manuscript and the figures. Ingrid Stolt carried out the assays and assisted in the statistical analyses.

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Authors and Affiliations

  1. Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, SE-751 85, Uppsala, Sweden

    Mary Kämpe, Christer Janson & Gunnemar Stålenheim

  2. Asthma Research Centre, Uppsala University, Uppsala, Sweden

    Mary Kämpe, Maria Lampinen, Ingrid Stolt, Christer Janson, Gunnemar Stålenheim & Marie Carlson

  3. Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden

    Maria Lampinen, Ingrid Stolt & Marie Carlson

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  1. Mary Kämpe
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Correspondence to Mary Kämpe.

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Kämpe, M., Lampinen, M., Stolt, I. et al. PI3-Kinase Regulates Eosinophil and Neutrophil Degranulation in Patients with Allergic Rhinitis and Allergic Asthma Irrespective of Allergen Challenge Model. Inflammation 35, 230–239 (2012). https://doi.org/10.1007/s10753-011-9309-5

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