Increased Expression of High Affinity IgE (Fc ɛ RI) Receptor- α Chain mRNA and Protein-bearing Eosinophils in Human Allergen-induced Atopic Asthma

Abstract

FcepsilonRI receptors play an important role in allergen-induced mediator release and antigen presentation by mast cells, basophils, and monocyte/macrophages in atopic disorders. The expression of FcepsilonRI by tissue eosinophils in atopic asthma after allergen challenge has not been established. For this reason we attempted to identify mRNA and protein product + FcepsilonRIalpha eosinophils in cytospins made from bronchoalveolar lavage (BAL) from atopic asthmatics (n = 9) and nonatopic normal subjects (n = 4) 24 h after segmental challenge with allergen or diluent. Messenger RNA for FcepsilonRIalpha was determined using in situ hybridization and FcepsilonRIalpha protein expression by immunocytochemistry using a mouse monoclonal antibody 22E7. Colocalization of FcepsilonRIalpha receptors to eosinophils was performed using chromotrope 2R. When compared with a control challenge, segmental challenge with Dermatophagoides pteronyssinus induced significant BAL eosinophilia (p = 0.007). The total number of BAL FcepsilonRIalpha mRNA and protein-positive cells also increased in asthmatics, median values 2 (0.7-7.2) and 11.5 (0.6-65.0) x 10(6) cells (p = 0.02) and 0 (0-0.3 x 10(6)) and 3.1 x 10(6) (0.45 - 162.5 x 10(6)) cells (p = 0.007), respectively, for mRNA and protein. Net increases in FcepsilonRIalpha+ cells correlated with the net increases in BAL eosinophils (r = 0.98, p = 0.0001 for mRNA and r = 0.72, p = 0.02 for protein). Colocalization studies with chromotrope 2R revealed that only 4% of FcepsilonRIalpha+ cells were eosinophils after control challenge and, in contrast, 85 to 95% of FcepsilonRIalpha+ cells were eosinophils after allergen. There were no differences in the numbers of FcepsilonRIalpha+ cells or eosinophils in normal control subjects. Our results demonstrated that local endobronchial allergen provocation in atopic asthmatics results in increased synthesis and expression of FcepsilonRIalpha predominantly on BAL eosinophils.

The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

“…Immunohistochemical and immunocytochemical studies carried out in patients with allergic diseases showed that the local allergen challenge induces the expression of FceRI on eosinophils infiltrating the respiratory system [74] and skin [75,76]. Moreover, the presence of FceRI was also confirmed on peripheral eosinophils in patients with various forms of allergic diseases [77].…”

Current and future biomarkers in allergic asthma

“…In the lung, the response to allergen challenge can be characterized by the infiltration of eosinophils expressing CD244 (148) and FceR1a (149)(150)(151) and in the late-phase response also CD25 and CD62L (152). Of note, the IL-5Ra (CD125) expression drops on eosinophils following allergen challenge (153).…”

The role of antigen presenting cells at distinct anatomic sites: they accelerate and they slow down allergies

“…The cytokine milieu in the airway environment at the time of exposure is crucial in the process of DC activation and maturation. As important mediators of the cellular recruitment process, chemokines such as TARC and MDC are present in high amounts in the mucosal tissue of the respiratory tract and promote the recruitment of distinct cell types acting in allergic inflammation, such as DC and CD4 + T-cells (35)(36)(37). The contact with allergens sets off a series of events that supply DC with the necessary equipment to migrate to the regional lymph nodes and activate allergen specific Th2 cells (38).…”