Introduction
Molecular Mechanism of IgE/FcεRI-Mediated Activation of MCs
Strategy | Pharmaceutical agents/Abs | Description/mechanism of action | Ref |
---|---|---|---|
Anti-IgE monoclonal antibodies | Omalizumab | Recombinant humanized anti-IgE mAb, also known as Xolair® Approved by FDA for the treatment of mild allergic asthma Mechanism of action: binds to free IgE and decreases the availability of IgE available to interact with FcεRI Omalizumab has no interference with receptor-bound IgE | |
Ligelizumab (QGE031) | Humanized IgG1 mAb with ability to binding to the Cε3 domain of IgE | [59] | |
Quilizumab | Structurally is a humanized, monoclonal IgG1 antibody with the ability to bind membrane-bound but not soluble IgE due to the absence of M1-prime segment in soluble IgE | [60] | |
Designed ankyrin repeat proteins (DARPins) | DARPin E2_79 | Acts by preventing IgE-FcεRI binding and disrupting preformed IgE-FcεRI complexes in vitro | [57] |
DARPin E3_54 | Inhibits IgE-FcεRI interaction | [57] | |
DARPin 30/85 | Bispecific molecule capable of binding to FcεRIα | [57] | |
Co-aggregation of FcεRI with the inhibitory FcγRIIb | GE2 | GE2 structurally is comprised of the hinge-Cγ2-Cγ3 domains from IgG Fc linked to Cε2-Cε4 domains of human IgE Fc Inhibits the phosphorylation of Syk | [57] |
MC Expression and Degranulation by TLRs and Lectin Receptors
MC Activation by Complement Receptors and Other GPCRs
Mediator | Receptor, interaction, and results | Ref |
---|---|---|
SCF | Binds to c-KIT (CD117), induces MC differentiation, survival, and release of pro-inflammatory cytokines, mainly IL-6, IL-8, and TNF-α | |
IL-33 | Acts through ST2 and induces the release of CCL4 and CXCL8 | [63] |
Substance P | Acts through NK1R and induces the release of IL-17 and histamine | |
Nerve growth factor (NGF) | Binds to TrkA, induces MC hyperplasia and cytokine production Induces the release of β-hexosaminidase in mice peritoneal MC | [65] [66] |
Calcitonin gene-related peptide (CGRP) | Acts through CGRPR and induces serotonin release | [67] |