A concept of soluble receptors in bronchial asthma

Functioning of soluble receptors, mainly soluble cytokine receptors, has been of interest to researchers since the last decade of the 20th century. Allergists’ interest in the issues of soluble receptors is relevant to our studies in the pathogenesis of bronchial asthma (BA), specifically, development of ectopic chemosensory signaling systems, including ectopic bitter taste receptors Tas2R, and signaling pathways of the Receptor for Advanced Glycation End products (RAGE). The expression of soluble receptors in BA was investigated in both studies. The article discusses the mechanisms of soluble receptor formation: 1) proteolytic cleavage of existing membrane receptors; 2) synthesis and release of soluble receptors lacking a transmembrane domain via alternative mRNA splicing; 3) release of membrane receptors in exosomes. Possible functional effects of soluble receptors are considered, i.e., neutralization of corresponding ligands (decoy receptors), ligand transport, ligand stabilization, and binding of membrane proteins. The results of studies of soluble receptors in health and disease are sometimes contradictory and not fully understood. Soluble receptors may be considered prospective therapeutic agents. Our previous data concerning probable functions of a number of soluble Tas2R38, Tas2R31, Tas2R5 receptors are considered when studying the patients with asthma in view of earlier knowledge of the soluble receptors functioning. The most important characteristics of the soluble receptors studied in BA are: 1) lower plasma levels of all discussed Tas2Rs in allergic asthma compared to nonallergic forms; 2) an inverse correlation between plasma Tas2R levels and bronchial resistance; 3) correlation of Tas2Rs with monocyte-macrophages, granulocytes and bronchial ciliated cells. The regulatory role of soluble receptors involved in asthma pathogenesis, mainly cytokines, as well as sTas2R and sRAGE, can be viewed through the corresponding membrane receptor functions. In this case, soluble forms of receptors play the role of decoy proteins that block functions mediated by membrane receptors. In this approach, the discussed soluble cytokine receptors and sRAGE have a positive regulatory effect in BA, whereas sTas2R exert negative action. The balance of soluble and membrane-bound receptor functions in cells involved in asthma pathogenesis is crucial for developing the novel therapies for asthma by targeting the Tas2R and RAGE receptors.