Regulation of the pleiotropic effects of tissue-resident mast cells

Abstract

Mast cells (MCs), which are best known for their detrimental role in patients with allergic diseases, act in a diverse array of physiologic and pathologic functions made possible by the plurality of MC types. Their various developmental avenues and distinct sensitivity to (micro-) environmental conditions convey extensive heterogeneity, resulting in diverse functions. We briefly summarize this heterogeneity, elaborate on molecular determinants that allow MCs to communicate with their environment to fulfill their tasks, discuss the protease repertoire stored in secretory lysosomes, and consider different aspects of MC signaling. Furthermore, we describe key MC governance mechanisms (ie, the high-affinity receptor for IgE [FcεRI]), the stem cell factor receptor KIT, the IL-4 system, and both Ca 21and phosphatase-dependent mechanisms. Finally, we focus on distinct physiologic functions, such as chemotaxis, phagocytosis, host defense, and the regulation of MC functions at the mucosal barriers of the lung, gastrointestinal tract, and skin. A deeper knowledge of the pleiotropic functions of MC mediators, as well as the molecular processes of MC regulation and communication, should enable us to promote beneficial MC traits in physiology and suppress detrimental MC functions in patients with disease. (J Allergy Clin Immunol 2019;144:S31-45.)

Mast cells: Promoters of health and modulators of disease

“…Different types of MCs have experienced different conditions during differentiation, such as contact with different integrins at their destination tissues or exposure to different cytokines. Important new research reviewed by Huber et al 6 identified transient receptor potential and ORAI Ca 21 channels, essential elements of Ca 21 -dependent MC activation in response to FcεRI clustering, as crucially regulating MC protease content and affecting FcεRI and KIT receptor signaling and responsiveness to IL-4 and other activity-modulating factors in mice. Furthermore, MRGPRX2 was identified as a receptor for secretagogues and small-molecule compounds triggering Ca 21 just 3 years ago.…”

Analysis of Mrgprb2 Receptor-Evoked Ca2+ Signaling in Bone Marrow Derived (BMMC) and Peritoneal (PMC) Mast Cells of TRPC-Deficient Mice

“…A more detailed characterization of the inward current through these channels revealed that it has a ratio of Ca 2+ to Na + permeability (P Ca /P Na ) of 0.55. All seven members of the TRPC subgroup of Transient Receptor Potential (TRP) channel protein family were reported to be expressed in several types of mast cells [for review see (14,22)]. As TRPC channels represent receptor-operated non-selective cation channels that can be activated by stimulation of various G q/11coupled receptors, it can be speculated whether TRPCs might be involved downstream of Mrgprb2 activation by agonists such as compound 48/80.…”

Molecular Biological Peculiarities of the Must Cells Secretome of the Lower Limb Skin in Trophic Ulcers of Various Etiologies

“…[17,18]. ТК принимают непосредственное участие в формировании патологических состояний посредством многочисленных компонентов секретома с высокой биологической активностью [20,32,33]. Учитывая известное селективное влияние триптазы ТК на главные патогенетические звенья реализации острого и хронического воспаления, исследование ее биологии в деятельности соединительной ткани кожи при имеющихся трофических нарушениях представляет особое значение в хирургии [7].…”