Review
Mast cells and inflammation

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Abstract

Mast cells are well known for their role in allergic and anaphylactic reactions, as well as their involvement in acquired and innate immunity. Increasing evidence now implicates mast cells in inflammatory diseases where they are activated by non-allergic triggers, such as neuropeptides and cytokines, often exerting synergistic effects as in the case of IL-33 and neurotensin. Mast cells can also release pro-inflammatory mediators selectively without degranulation. In particular, IL-1 induces selective release of IL-6, while corticotropin-releasing hormone secreted under stress induces the release of vascular endothelial growth factor. Many inflammatory diseases involve mast cells in cross-talk with T cells, such as atopic dermatitis, psoriasis and multiple sclerosis, which all worsen by stress. How mast cell differential responses are regulated is still unresolved. Preliminary evidence suggests that mitochondrial function and dynamics control mast cell degranulation, but not selective release. Recent findings also indicate that mast cells have immunomodulatory properties. Understanding selective release of mediators could explain how mast cells participate in numerous diverse biologic processes, and how they exert both immunostimulatory and immunosuppressive actions. Unraveling selective mast cell secretion could also help develop unique mast cell inhibitors with novel therapeutic applications. This article is part of a Special Issue entitled: Mast cells in inflammation.

Research Highlights

► Mast cells release pro-inflammatory mediators selectively without degranulation. ► Mast cells are activated by CRH released under stress. ► Neuropeptide mast cell triggers have synergistic action with cytokines, like IL-33. ► Unique flavonoid combinations can effectively block mast cell secretion. ► Mast cells may serve as new therapeutic targets for psoriasis and multiple sclerosis.

Abbreviations

AD
atopic dermatitis
BBB
blood–brain barrier
Bcl10–Malt1
B cell lymphoma 10–Mucosal-associated lymphoid tissue 1
BDNF
brain-derived neurotrophic factor
CRH
corticotropin-releasing hormone
CRHR
corticotropin-releasing hormone receptor
Drp1
dynamin related protein 1
EAE
experimental allergic encephalomyelitis
FcεRI
high affinity surface receptors for IgE
GM-CSF
granulocyte-macrophage colony-stimulating factor
hCBMCs
human umbilical cord-derived mast cells
HPA
hypothalamic–pituitary–adrenal
IFN
interferon
IL
interleukin
LPS
lipopolysaccharide
LT
leukotriene
MBP
myelin basic protein
MCP-1
monocyte chemoattractant protein-1
MS
multiple sclerosis
MMP
matrix metalloproteinase
NGF
nerve-growth factor
NK
neurokinin
NT
neurotensin
PACAP
pituitary adenylate cyclase activating polypeptide
PAF
platelet activating factor
PAR
protease activated receptors
PI3-K
phosphatidylinositol 3-kinase
PTEN
phosphatase and tensin homologue
RANTES
regulated upon activation, normal T cell expressed and secreted
RBL
rat basophil leukemia
SCF
stem cell factor
SF-1α
stromal cell-derived factor-1 alpha
SLPI
secretory leukocyte protease inhibitor
SP
substance P
TGFβ
transforming growth factor β
TLR
toll-like receptor
TNF
tumor necrosis factor
TSLP
thymic stromal lymphopoietin
Ucn
urocortin
UCP2
uncoupling protein 2
VEGF
vascular endothelial growth factor
VIP
vasoactive intestinal peptide

Keywords

Skin inflammation
Mast cell
Multiple sclerosis
Selective release

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This article is part of a Special Issue entitled: Mast cells in inflammation.