CELLS OF THE IMMUNE SYSTEM

Basophils and Mast Cells


The 1908 Nobel Prize was awarded jointly to P. Ehrlich (Germany) and E.Metchnikoff (Russia) in recognition of their work in immunity. In addition, P.Ehrlich discovered mast cells.

Basophils and mast cells share the ability to degranulate rapidly and release histamine following high-affinity IgE receptor cross-linking (FcεRI), but they differ in their precursors, the capacity of generating inflammatory eicosanoids, and releasing immunomodulating cytokines and chemokines. Also, basophils leave the bone marrow mature, whereas the mast cells circulate throughout the body in an immature form, maturing once in a tissue site.

Mast cells are highly heterogeneous and divided into mast cells expressing tryptase and chymase (MCTC, "connective-tissue mast cells"), mast cells expressing only tryptase (MCTT, "atypical, or mucosal mast cells"), and the rare mast cells expressing only chymase (MCC).

Mast cell contains 50200 large granules that store three types of inflammatory mediators, which are rich in the following:
(1) preformed mediators released during the degranulation of mast cells and contain histamine, serotonin, dopamine, tryptase, chymase, heparin, chondroitin sulfate, TNF-α, IL-4, IL-15, TGF-β, CCL2 (MCP-1), CCL5 (RANTES), CCL7 (MCP-3), and chemotactic peptides for eosinophils and neutrophils;
(2) neoformed mediators secreted rapidly after preformed and include cysteinyl leukotrienes (LTC4, LTD4, and LTE4),) leukotriene B4 (LTB4), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), and platelet-activating factor (PAF);
(3) neosynthesized mediators released in a little time after preformed and contain a variety of cytokines and chemokines, growth factors, nitric oxide, and components of complement (C3 and C5).

Mast cells are leading cells of allergic inflammation. Upon exposure to an allergen in the unified airway, mast cells' degranulation leads to vascular permeability, local edema, bronchial and nasal obstruction, and cough. During exposure to an allergen in the gastrointestinal tract, the allergen permeates through the epithelial layer of the gut's mucosa and binds to IgE on mucosal mast cells. Mast cells respond, increasing the fluid secretion, smooth muscle contraction, skin itch, peristalsis, vomiting, and diarrhea.
IgE-independent activation of mast cells is provided through MRGPRX2 receptor. It leads to the release of pro-inflammatory cytokines and chemokines, migration of inflammatory cells and allergic inflammation development.

Mast cells are upregulated by type 9 helper T cells (IL-9, IL-10), type 2 helper T cells (IL-4, IL-9, IL-13, and particularly IL-33), and some chemokines, including CCL11 (Eotaxin--1), CCL24 (Eotaxin-2), and CCL26 (Eotaxin-3). On the other hand, mast cells play a role in the differentiation of type 2 helper T cells and follicular helper T cells.

For a long time, mast cells were viewed canonically as effector cells in allergic disorders. There is now evidence that they and their different products (soluble mediators, extracellular vesicles, and extracellular DNA traps) communicate with nearly all immune cells and neurons and contribute to the homeostasis of the immune and nervous systems, and take part in the host defense against pathogens, pathogenesis of cancer, and other pathologic processes.

©V.V.Klimov