Abstract
Mast
cells (MCs) are tissue resident immune cells that are best known for
their roles in allergic and inflammatory diseases. In addition to the
high affinity IgE receptor (FcεRI), MCs express numerous G protein
coupled receptors (GPCRs), which are the most common targets of drug
therapy.
Neurokinin 1 receptor (NK-1R) is expressed on MCs and
contributes to IgE and non-IgE-mediated responses in mice. Although
NK-1R antagonists are highly effective in modulating experimental
allergic and inflammatory responses in mice they lack efficacy in
humans. This article reviews recent findings that demonstrate that while
neuropeptides (NPs) activate murine MCs via NK-1R and Mas related G
protein coupled receptor B2 (MrgprB2), they activate human MCs via
Mas-related G protein coupled receptor X2 (MRGPRX2). Interestingly,
conventional NK-1R antagonists have off-target activity against mouse
MrgprB2 but not human MRGPRX2. These findings suggest that the failure
to translate studies with NK-1R antagonists from in vivo mouse
studies to the clinic likely reflects their lack of effect on human
MRGPRX2. A unique feature of MRGPRX2 that distinguishes it from other
GPCRs is that it is activated by a diverse group of ligands that
include; neuropeptides, cysteine proteases, antimicrobial peptides and
cationic proteins released from activated eosinophils. Thus, the
development of small molecule MRGPRX2-specific antagonists or
neutralizing antibodies may provide new targets for the treatment of
MC-mediated allergic and inflammatory diseases.
Keywords: Mast cells, NK-1R, MrgprB2, MRGPRX2, anaphylaxis, asthma
Ang(1-7) muodostaa RAAS systeemiin protektiivisen siiven, josta on vähemmäntietoa, muta SARS2 nujertaa tämän protektiivisen siiven.
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