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International Journal of Molecular... Oct 2021Mast cells are derived from hematopoietic stem cell precursors and are essential to the genesis and manifestations of the allergic response. Activation of these cells by... (Review)
Review
Mast cells are derived from hematopoietic stem cell precursors and are essential to the genesis and manifestations of the allergic response. Activation of these cells by allergens leads to degranulation and elaboration of inflammatory mediators, responsible for regulating the acute dramatic inflammatory response seen. Mast cells have also been incriminated in such diverse disorders as malignancy, arthritis, coronary artery disease, and osteoporosis. There has been a recent explosion in our understanding of the mast cell and the associated clinical conditions that affect this cell type. Some mast cell disorders are associated with specific genetic mutations (such as the D816V gain-of-function mutation) with resultant clonal disease. Such disorders include cutaneous mastocytosis, systemic mastocytosis (SM), its variants (indolent/ISM, smoldering/SSM, aggressive systemic mastocytosis/ASM) and clonal (or monoclonal) mast cell activation disorders or syndromes (CMCAS/MMAS). Besides clonal mast cell activations disorders/CMCAS (also referred to as monoclonal mast cell activation syndromes/MMAS), mast cell activation can also occur secondary to allergic, inflammatory, or paraneoplastic disease. Some disorders are idiopathic as their molecular pathogenesis and evolution are unclear. A genetic disorder, referred to as hereditary alpha-tryptasemia (HαT) has also been described recently. This condition has been shown to be associated with increased severity of allergic and anaphylactic reactions and may interact variably with primary and secondary mast cell disease, resulting in complex combined disorders. The role of this review is to clarify the classification of mast cell disorders, point to molecular aspects of mast cell signaling, elucidate underlying genetic defects, and provide approaches to targeted therapies that may benefit such patients.
Topics: Animals; Humans; Mast Cell Activation Disorders; Mast Cells; Mastocytosis
PubMed: 34681933
DOI: 10.3390/ijms222011270 -
The Journal of Histochemistry and... Oct 2014Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed as effectors of allergy. It has been only in the past two decades that mast cells have... (Review)
Review
Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed as effectors of allergy. It has been only in the past two decades that mast cells have gained recognition for their involvement in other physiological and pathological processes. Mast cells have a widespread distribution and are found predominantly at the interface between the host and the external environment. Mast cell maturation, phenotype and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of an array of biologically active mediators. These features enable mast cells to act as both first responders in harmful situations as well as to respond to changes in their environment by communicating with a variety of other cells implicated in physiological and immunological responses. Therefore, the critical role of mast cells in both innate and adaptive immunity, including immune tolerance, has gained increased prominence. Conversely, mast cell dysfunction has pointed to these cells as the main offenders in several chronic allergic/inflammatory disorders, cancer and autoimmune diseases. This review summarizes the current knowledge of mast cell function in both normal and pathological conditions with regards to their regulation, phenotype and role.
Topics: Animals; Disease; Humans; Mast Cells; Phenotype
PubMed: 25062998
DOI: 10.1369/0022155414545334 -
European Journal of Pharmacology May 2016Mast cells play a critical role in type 1 hypersensitivity reactions. Indeed, mast cell mediators are implicated in many different conditions including allergic... (Review)
Review
Mast cells play a critical role in type 1 hypersensitivity reactions. Indeed, mast cell mediators are implicated in many different conditions including allergic rhinitis, conjunctivitis, asthma, psoriasis, mastocytosis and the progression of many different cancers. Thus, there is intense interest in the development of agents which prevent mast cell mediator release or which inhibit the actions of such mediators once released into the environment of the cell. Much progress into the design of new agents has been made since the initial discovery of the mast cell stabilising properties of khellin from Ammi visnaga and the clinical approval of cromolyn sodium. This review critically examines the progress that has been made in the intervening years from the design of new agents that target a specific signalling event in the mast cell degranulation pathway to those agents which have been developed where the precise mechanism of action remains elusive. Particular emphasis is also placed on clinically used drugs for other indications that stabilise mast cells and how this additional action may be harnessed for their clinical use in disease processes where mast cells are implicated.
Topics: Animals; Cell Degranulation; Drug Discovery; Humans; Mast Cells; Signal Transduction
PubMed: 26130122
DOI: 10.1016/j.ejphar.2015.05.071 -
The Journal of Allergy and Clinical... Aug 2017Mast cell activation is common and possibly necessary for maintenance of survival. Disordered mast cell activation occurs when mast cells are pathologically overproduced... (Review)
Review
Mast cell activation is common and possibly necessary for maintenance of survival. Disordered mast cell activation occurs when mast cells are pathologically overproduced or if their activation is out of proportion to the perceived threat to homeostasis. Mast cell activation syndrome refers to a group of disorders with diverse causes presenting with episodic multisystem symptoms as the result of mast cell mediator release. Despite introduction of diagnostic criteria and some advances in treatment in the last decade, many areas of mast cell activation syndrome are in need of research. This article reviews our current knowledge about the various types of mast cell activation disorders, their treatment, and areas of uncertainty in need of future investigation.
Topics: Humans; Immune System Diseases; Mast Cells; Syndrome
PubMed: 28780942
DOI: 10.1016/j.jaci.2017.06.007 -
Surgical Pathology Clinics Dec 2023Pathologists are increasingly asked to evaluate mast cell infiltrates in the gastrointestinal tract when there is clinical concern for systemic mastocytosis or a variety... (Review)
Review
Pathologists are increasingly asked to evaluate mast cell infiltrates in the gastrointestinal tract when there is clinical concern for systemic mastocytosis or a variety of functional disorders, including irritable bowel syndrome and mast cell activation syndrome. Neoplastic mast cells have established quantitative, morphologic, and immunohistochemical features that facilitate their identification in gastrointestinal mucosal biopsies. Specific qualitative and quantitative findings are lacking for inflammatory mast cell-mediated disorders. This review covers histopathologic features of mast cell disorders that affect the gastrointestinal tract and offers practical guidance for their assessment in mucosal biopsies.
Topics: Humans; Mast Cells; Gastrointestinal Tract; Mastocytosis; Mastocytosis, Systemic; Biopsy
PubMed: 37863564
DOI: 10.1016/j.path.2023.05.010 -
Journal of Immunoassay & Immunochemistry Jul 2020Mast cells (MCs) are well known for their role in allergic conditions. This cell can be activated by various types of secretagogues, ranging from a small chemical to a... (Review)
Review
Mast cells (MCs) are well known for their role in allergic conditions. This cell can be activated by various types of secretagogues, ranging from a small chemical to a huge protein. Mast cell activation by secretagogues triggers the increase in intracellular calcium (iCa) concentration, granule trafficking, and exocytosis. Activated mast cells release their intra-granular pre-stored mediator or the newly synthesized mediator in the exocytosis process, in the form of degranulation or secretion. There are at least three types of exocytosis in mast cells, which are suggested to contribute to the release of different mediators, i.e.,, piecemeal, kiss-and-run, and compound exocytosis. The status of mast cells, i.e., activated or resting, is often determined by measuring the concentration of the released mediator such as histamine or β-hexosaminidase. This review summarizes several mast cell components that have been and are generally used as mast cell activation indicator, from the classical histamine and β-hexosaminidase measurement, to eicosanoid and granule trafficking observation. Basic principle of the component determination is also explained with their specified research application and purpose. The information will help to predict the experiment results with a certain study design.
Topics: Animals; Biomarkers; Histamine; Humans; Mast Cells; beta-N-Acetylhexosaminidases
PubMed: 32501748
DOI: 10.1080/15321819.2020.1769129 -
International Journal of Molecular... Aug 2019Mast cells are well accepted as important sentinel cells for host defence against selected pathogens. Their location at mucosal surfaces and ability to mobilize multiple... (Review)
Review
Mast cells are well accepted as important sentinel cells for host defence against selected pathogens. Their location at mucosal surfaces and ability to mobilize multiple aspects of early immune responses makes them critical contributors to effective immunity in several experimental settings. However, the interactions of mast cells with viruses and pathogen products are complex and can have both detrimental and positive impacts. There is substantial evidence for mast cell mobilization and activation of effector cells and mobilization of dendritic cells following viral challenge. These cells are a major and under-appreciated local source of type I and III interferons following viral challenge. However, mast cells have also been implicated in inappropriate inflammatory responses, long term fibrosis, and vascular leakage associated with viral infections. Progress in combating infection and boosting effective immunity requires a better understanding of mast cell responses to viral infection and the pathogen products and receptors we can employ to modify such responses. In this review, we outline some of the key known responses of mast cells to viral infection and their major responses to pathogen products. We have placed an emphasis on data obtained from human mast cells and aim to provide a framework for considering the complex interactions between mast cells and pathogens with a view to exploiting this knowledge therapeutically. Long-lived resident mast cells and their responses to viruses and pathogen products provide excellent opportunities to modify local immune responses that remain to be fully exploited in cancer immunotherapy, vaccination, and treatment of infectious diseases.
Topics: Animals; Bacteria; Culicidae; Humans; Immunity; Mast Cells; Models, Biological; Viruses
PubMed: 31480219
DOI: 10.3390/ijms20174241 -
Canadian Journal of Physiology and... Jun 1984Increasing evidence for the existence of inter- and intra-species mast cell heterogeneity has expanded the potential biological role of this cell. Early studies... (Review)
Review
Increasing evidence for the existence of inter- and intra-species mast cell heterogeneity has expanded the potential biological role of this cell. Early studies suggesting that mast cells at mucosal sites differ morphologically and histochemically from connective tissue mast cells have been confirmed using isolated intestinal mucosal mast cells in the rat and more recently in man. These studies also established that mucosal mast cells are functionally distinct from connective tissue mast cells. Thus, mucosal and connective tissue mast cells differ in their responsiveness to a variety of mast cell secretagogues and antiallergic agents. Speculation about the therapeutic use of antiallergic drugs in disorders involving intestinal mast cells cannot, therefore, be based on extrapolation from studies of their effects on mast cells from other sites. Regulatory mechanisms for mast cell secretion may also be heterogeneous since mucosal mast cells differ from connective tissue mast cells in their response to a variety of physiologically occurring regulatory peptides. The development of techniques to purify isolated mast cell subpopulations will facilitate future analysis of the biochemical basis of the functional heterogeneity of mast cells.
Topics: Animals; Connective Tissue Cells; Endorphins; Histamine Release; Humans; Intestinal Mucosa; Mast Cells; Nerve Tissue Proteins
PubMed: 6204731
DOI: 10.1139/y84-121 -
Cells Mar 2021Mast cells are essential first responder granulocytes in the innate immune system that are well known for their role in type 1 immune hypersensitivity reactions.... (Review)
Review
Mast cells are essential first responder granulocytes in the innate immune system that are well known for their role in type 1 immune hypersensitivity reactions. Although mostly recognized for their role in allergies, mast cells have a range of influences on other systems throughout the body and can respond to a wide range of agonists to properly prime an appropriate immune response. Mast cells have a dynamic energy metabolism to allow rapid responsiveness to their energetic demands. However, our understanding of mast cell metabolism and its impact on mast cell activation and development is still in its infancy. Mast cell metabolism during stimulation and development shifts between both arms of metabolism: catabolic metabolism-such as glycolysis and oxidative phosphorylation-and anabolic metabolism-such as the pentose phosphate pathway. The potential for metabolic pathway shifts to precede and perhaps even control activation and differentiation provides an exciting opportunity to explore energy metabolism for clues in deciphering mast cell function. In this review, we discuss literature pertaining to metabolic environments and fluctuations during different sources of activation, especially IgE mediated vs. non-IgE mediated, and mast cell development, including progenitor cell types leading to the well-known resident mast cell.
Topics: Cell Differentiation; Energy Metabolism; Humans; Mast Cells
PubMed: 33801300
DOI: 10.3390/cells10030524 -
International Journal of Molecular... Sep 2019The pathophysiological roles of mast cells are still not fully understood, over 140 years since their description by Paul Ehrlich in 1878. Initial studies have attempted... (Review)
Review
The pathophysiological roles of mast cells are still not fully understood, over 140 years since their description by Paul Ehrlich in 1878. Initial studies have attempted to identify distinct "subpopulations" of mast cells based on a relatively small number of biochemical characteristics. More recently, "subtypes" of mast cells have been described based on the analysis of transcriptomes of anatomically distinct mouse mast cell populations. Although mast cells can potently alter homeostasis, in certain circumstances, these cells can also contribute to the restoration of homeostasis. Both solid and hematologic tumors are associated with the accumulation of peritumoral and/or intratumoral mast cells, suggesting that these cells can help to promote and/or limit tumorigenesis. We suggest that at least two major subsets of mast cells, MC1 (meaning anti-tumorigenic) and MC2 (meaning pro-tumorigenic), and/or different mast cell mediators derived from otherwise similar cells, could play distinct or even opposite roles in tumorigenesis. Mast cells are also strategically located in the human myocardium, in atherosclerotic plaques, in close proximity to nerves and in the aortic valve. Recent studies have revealed evidence that cardiac mast cells can participate both in physiological and pathological processes in the heart. It seems likely that different subsets of mast cells, like those of cardiac macrophages, can exert distinct, even opposite, effects in different pathophysiological processes in the heart. In this chapter, we have commented on possible future needs of the ongoing efforts to identify the diverse functions of mast cells in health and disease.
Topics: Animals; Biomarkers; Cell Movement; Cell Physiological Phenomena; Disease Susceptibility; Homeostasis; Humans; Mast Cells
PubMed: 31500217
DOI: 10.3390/ijms20184397