Allergic diseases that occurs according to the mechanism of type I hypersensitivity are caused by production of IgE (IgE) to harmless allergens. Among these diseases, which often not only reduce the quality of life, but also in some cases pose a mortal danger to patients in case of failure to provide timely qualified help, respiratory diseases such as bronchial asthma and allergic rhinitis take a special place due to its severity of the manifestation.According to one of the leading hypotheses, one of the reasons for the significant increase in the prevalence of these diseases in various countries, including Russia, is the air pollution with microheterogeneous (size from 0.1 to 10 microns) and larger polydisperse urban dust particles and diesel exhaust particles.Particles of urban industrial dust contain heavy metals, and particles of diesel exhaust, in addition, polycyclic aromatic hydrocarbons and their nitro derivatives, which have cytotoxic and carcinogenic properties.In this regard, these particles can interact with the cells of the barrier epithelium of the lung alveoli and alveolar macrophages, stimulating the local production of pro-inflammatory cytokines and chemokines.
The new literature data presented by us in the review, as well as our own results obtained during the development of an innovative clinically relevant model of allergy, indicate that the administration of low antigen doses behind the barrier triggers local B-cell IgE switching in the tissue, but not in the regional lymph nodes draining this tissue.New literature data show that when monodisperse particles with uniform chemical composition (silicon, hydroxyappatite, particles of aluminum and nickel oxides) enter the lungs, the formation of broncho-associated lymphoid clusters is induced, and the production of allergen-specific IgE is mainly occurred in these structures.However, the effect of multicomponent polydisperse particles in this regard has not yet been studied.In addition, although it is well defined thatair-pollutant particles can activatevarious signaling pathways in lung epithelial cells, a systematic study of the contribution of these pathways to the induction of local inflammation and the formation of broncho-associated lymphoid clusters, and most importantly, to the adjuvant effect of such particles in relation to the production of allergen-specific antibodies have not been studied.Thus, the originality of the work will be the investigation of the effect of different samples of multicomponent polydisperse particles of aeropollutants not only on local inflammation in general, but on its specific component - local production of allergen-specific antibodies.In addition, for the first time, the effect of blocking various signaling pathways and cellular stress mechanisms — genotoxic, oxidative, endoplasmic reticulum stress — on the local and systemic humoral response will be compared.
The results of the project will confirm or refute the adjuvant effect of various standardized samples of particles of airborne pollutants on the local and systemic production of allergen-specific antibodies, as well as confirm or refute the role of the basic mechanisms of cell stress (genotoxic, oxidative, endoplasmic reticulum stress) and signaling pathways in the studied process.In addition to substantial fundamental significance, the data will also have vital practical significance, since they will lay the foundation for the future development of etiotropic therapy and prevention of allergic diseases in patients in large and (or) environmentally disadvantaged cities.