IgE-dependent signaling as a therapeutic target for allergies

Abstract

Atopic diseases are complex, with many immunological participants, but the central element in their expression is IgE antibody. In an atopic individual, the immune system pathologically reacts to environmental substances by producing IgE, and these allergen-specific IgE antibodies confer to IgE receptor-bearing cells responsiveness to the environmental substances. Mast cells and basophils are central to the immediate hypersensitivity reaction that is mediated by IgE. In humans, there are various other immune cells, notably dendritic cells and B cells, which can also bind IgE. For mast cells, basophils and dendritic cells, the receptor that binds IgE is the high affinity receptor, FcεRI. For B cells and a few other cell types, the low affinity receptor, FcεRII, provides the cell a means to sense the presence of IgE. This overview will focus on events following activation of the high-affinity receptor because FcεRI generates the classical immediate hypersensitivity reaction.

Cholinergic neurotransmission links solitary chemosensory cells to nasal inflammation

“…The best described airway proinflammatory pathway is IgEmediated type I immune hypersensitivity, which underlies allergic rhinitis (31). Typically, the xenobiotics that activate the IgE pathway are large macromolecules, such as proteins in pollen (31).…”

“…Typically, the xenobiotics that activate the IgE pathway are large macromolecules, such as proteins in pollen (31).…”

“…Mast cells have been implicated in the recruitment of other immune cells (37)(38)(39), and therefore, mast cell degranulation could recruit other elements of the innate immune system to fight invasive bacteria and prevent additional damage to the epithelium. Many of the mediators released from mast cells have a synergistic effect on inflammation, creating positive feedback, which could lead to pathological inflammation (12,31,40) …”

Antiallergic and Antiasthmatic Effects of a Novel Enhydrazinone Ester (CEE-1): Inhibition of Activation of Both Mast Cells and Eosinophils

“…It has been established that both of these events are critical steps in the signaling pathways of activation for both mast cells and eosinophils (Adcock et al, 2008;MacGlashan, 2012;Shamri et al, 2013). Although CEE-1 failed to block C5a-induced increase in intracellular Ca 21 concentration, it significantly attenuated the phosphorylation of both ERK1/2 and p38-MAPK, thus suggesting that the drug may produce its effect by blocking the phosphorylation of these critical MAP kinases.…”

“…For example, the earliest event in the stimulusresponse coupling in the two cell types is the phosphorylation and activation of the Src tyrosine kinases Lyn and Syk (Adcock et al, 2008;MacGlashan, 2012). This is followed by the downstream activation of phospholipase C and mitogen-activated protein kinases (MAPKs), such as extracellular signalregulated kinases (ERK)1/2 and p38-MAP kinases (Duan and Wong, 2006;Adcock et al, 2008;Shamri et al, 2013).…”