Signaling through the high affinity IgE receptor and conditions able to modify IgE‐antigen responsiveness of mast cells

Abstract

Signaling through the high affinity receptor for IgE (FceRI) on mast cells comprises an intricate network of protein-protein modifications and interactions leading to mast cell degranulation, lipid-derived mediator production and cytokine release. Depending on the tissue where mast cells are activated, mediator release can induce distinct allergy symptoms. FceRI receptor mainly couples to at least two Src family kinases (Lyn and Fyn), which are responsible for the initiation of the signaling cascade. Distinct membrane bound adapters couple the initial signal to the formation of particular multi-molecular complexes that, in turn, will mediate a specific final response. In this review we summarize the molecular mechanisms initiated by the FceRI receptor on mast cells that have been involved in cytokine expression. At the same time, some conditions where the main signal transduction mechanism is modified will be analyzed in order to understand how locally produced mediators could alter IgE-antigen-induced allergic responses.

Controlling Mast Cell Activation and Homeostasis: Work Influenced by Bill Paul That Continues Today

“…Many of the pathways controlling FcεRI-induced mast cell activation have been described in detail, and we direct the reader to other recent reviews ( 61 – 63 ). However, some aspects of FcεRI activation warrant special attention here.…”

TGF Presence During IgE-dependent Sensitization Primes Mast Cells for Higher VEGF Production After Fc RI Activation

“…One of the more distinctive characteristics of the Fc RI signal transduction system is the capacity of coupling to specific cellular effectors depending on the particular composition of the multimolecular complexes formed at the plasma membrane [6], this important feature suggest that, potentially, signaling could be modulated by the presence of different locally-produced mediators surrounding mast cells. Those cytokines, growth factors or neurotransmitters, acting on mast cells, could alter the availability of signaling mole-cules in different complexes, or produce positive/negative regulators of the Fc RI signaling pathway [7]. TGF s are regulatory cytokines with pleiotropic effects on cell proliferation, differentiation, migration and survival, affecting multiple biological processes including development, fibrosis, wound healing, and immune responses [8].…”