Regulation of the High Affinity IgE Receptor (FcεRI) in Human Neutrophils: Role of Seasonal Allergen Exposure and Th-2 Cytokines

Martin P. Alphonse,Lianyu Shan,F. Estelle R. Simons,Kent T. HayGlass,Arash S. Saffar,Abdelilah S. Gounni,Marta Feldmesser

doi:10.1371/journal.pone.0001921

Abstract

The high affinity IgE receptor, FcεRI, plays a key role in the immunological pathways involved in allergic asthma. Previously we have demonstrated that human neutrophils isolated from allergic asthmatics express a functional FcεRI, and therefore it was of importance to examine the factors regulating its expression. In this study, we found that neutrophils from allergic asthmatics showed increased expression of FcεRI-α chain surface protein, total protein and mRNA compared with those from allergic non asthmatics and healthy donors (p<0.001). Interestingly, in neutrophils isolated from allergic asthmatics, FcεRI-α chain surface protein and mRNA expression were significantly greater during the pollen season than outside the pollen season (n = 9, P = 0.001), an effect which was not observed either in the allergic non asthmatic group or the healthy donors (p>0.05). Allergen exposure did not affect other surface markers of neutrophils such as CD16/FcγRIII or IL-17R. In contrast to stimulation with IgE, neutrophils incubated with TH2 cytokines IL-9, GM-CSF, and IL-4, showed enhanced FcεRI-α chain surface expression. In conclusion, these results suggest that enhanced FcεRI expression in human neutrophils from allergic asthmatics during the pollen season can make them more susceptible to the biological effects of IgE, providing a possible new mechanism by which neutrophils contribute to allergic asthma.

Highlights

Asthma is a chronic inflammatory disease of the bronchial airways which has been increasing in prevalence during the last four decades
Neutrophils from allergic asthmatics showed an increase in FceRI mRNA expression compared with allergic non asthmatic (22.968.08%, n = 18) or healthy individuals (10.1466.25 %, n = 21) (p,0.001, Figure 1A, B)
Real-time Reverse transcription (RT)-PCR analysis showed a significant increase of FceRIa chain mRNA in neutrophils from allergic asthmatics (n = 7) compared with healthy individuals (n = 10, p = 0.0046), but not allergic non asthmatics (n = 6, p.0.05, Figure 1F)

Summary

Introduction

Asthma is a chronic inflammatory disease of the bronchial airways which has been increasing in prevalence during the last four decades. Airway inflammation is a major factor in the pathogenesis of asthma, in associated bronchial hyperresponsiveness and in disease severity [1,2]. The inflammatory component of this disease includes an increased number of activated T lymphocytes, mast cells, neutrophils and eosinophils within the airway lumen and bronchial submucosa [3]. Many studies support the concept that neutrophils may significantly contribute to chronic inflammation and alterations in airway structure that characterize asthma. An increase of airway neutrophils was detected in induced sputum from adults with acute exacerbations of severe asthma, and in bronchial biopsies of severe steroid resistant asthmatics [7,8,9]. Circulating neutrophils are activated during active asthma, after exercise-induced bronchospasm and during both early and late asthmatic reactions induced by allergen [7]

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Conclusion