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Mast Cell Biology at Molecular Level: a Comprehensive Review

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Abstract

Mast cells (MCs) are portions of the innate and adaptive immune system derived from bone marrow (BM) progenitors that are rich in cytoplasmic granules. MC maturation, phenotype, and function are determined by their microenvironment. MCs accumulate at inflammatory sites associated with atopy, wound healing, and malignancies. They interact with the external environment and are predominantly located in close proximity of blood vessels and sensory nerves. MCs are key initiators and modulators of allergic, anaphylactic, and other inflammatory reactions, by induction of vasodilation, promoting of vascular permeability, recruitment of inflammatory cells, facilitation of adaptive immune responses, and modulation of angiogenesis, and fibrosis. They express a wide range of receptors, e.g., for IgE (FcεRI), IgG (FcγR), stem cell factor (SCF) (KIT receptor or CD117), complement (including C5aR), and cytokines, that upon activation trigger various signaling pathways. The final consequence of such ligand receptor–based activation of MCs is the release of a broad array of mediators which are classified in three categories. While some mediators are preformed and remain stored in granules such as heparin, histamine, and enzymes mainly chymase and tryptase, others are de novo synthesized only after activation including LTB4, LTD4, PDG2, and PAF, and the cytokines IL-10, IL-8, IL-5, IL-3, IL-1, GM-CSF, TGF-β, VEGF, and TNF-α. Depending on the stimulus, MCs calibrate their pattern of mediator release, modulate the amplification of allergic inflammation, and are involved in the resolution of the immune responses. Here, we review recent findings and reports that help to understand the MC biology, pathology, and physiology of diseases with MC involvement.

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Abbreviations

BM:

Bone marrow

CM:

Cutaneous mastocytosis

DAMPs:

Damage-associated molecular patterns

HCMCs:

Human cultured mast cells

JAK:

Janus kinase

LAT:

Linker for activator of T cells

LT:

Leukotriene

MC:

Mast cell

MCp:

Mast cell progenitor

NGF:

Nerve growth factor

PAMPs:

Pathogen-associated molecular patterns

PAR2:

Protease-activated receptor2

PG:

Prostaglandin

RER:

Rough endoplasmic reticulum

SCF:

Stem cell factor

SG:

Secretory granules

SM:

Systemic mastocytosis

SM-AHNMD:

SM with associated clonal hematological non–mast cell lineage disease

Syk:

Spleen tyrosine kinase

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Daniel Elieh Ali Komi

  2. Department of Immunology, Tabriz University of Medical Sciences, Tabriz, Iran

    Daniel Elieh Ali Komi

  3. Floridsdorf Allergy Center (FAZ), Vienna, Austria

    Stefan Wöhrl

  4. Department of Medicine and Ophthalmology, Hackensack Meridian School of Medicine at Seton Hall University, 400 Mountain Avenue, Springfield, NJ, 07081-2515, USA

    Leonard Bielory

  5. Department of Medicine, Thomas Jefferson Universi ty Sidney Kimmel School of Medicine, Philadelphia, PA, USA

    Leonard Bielory

  6. Rutgers University Center of Environmental Prediction, New Brunswick, NJ, USA

    Leonard Bielory

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  3. Leonard Bielory
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Daniel Elieh Ali Komi, Stefan Wöhrl, and Leonard Bielory have been directly involved in the preparation of the manuscript. Daniel Elieh Ali Komi has designed and created the figures. Leonard Bielory and Stefan Wöhrl have reviewed, revised, and added inputs.

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Correspondence to Leonard Bielory.

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Elieh Ali Komi, D., Wöhrl, S. & Bielory, L. Mast Cell Biology at Molecular Level: a Comprehensive Review. Clinic Rev Allerg Immunol 58, 342–365 (2020). https://doi.org/10.1007/s12016-019-08769-2

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