Abstract
Anafylactic reactions are mostly caused via the activation of the high affinity IgE receptor (FcεRI) on the surface of basophils and mast cells (classical pathway), or via the activation of the low affinity IgG receptor on the surface of macrophages (alternative pathway). Here we will focus on the classical pathway.
Aggregation of FcεRI itself initiates signalization cascades involving tens of proteins, among the physiological effects are degranulation and histamine release. Frequently underscored is the possibility of activation of basophils via number of surface receptors (CD28, CD137, CD226, Toll-like receptors, and integrins, etc.) modulating intensity of signal induced by FceRI aggregation.
Some surface molecules (c-kit, Thy-1, C3a receptor, etc.) are even able to activate basophils in absence of the parallel FceRI aggregation. In clinical or preclinical use is a number of inhibitors of unwanted activation of basophils during anaphylaxis.
Among them are inhibitors of tyrosine kinases - Gleevec, dasatinib, or semaxinib. Promising are also humanized monoclonal antibodies, fusion proteins and above all the epitope-specific peptides called mimotopes.