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Biochimica Et Biophysica Acta Jan 2012Mast cells are critical effectors in the development of allergic diseases and in many immunoglobulin E-mediated immune responses. These cells exert their physiological... (Review)
Review
Mast cells are critical effectors in the development of allergic diseases and in many immunoglobulin E-mediated immune responses. These cells exert their physiological and pathological activities by releasing granules containing histamine, cytokines, chemokines, and proteases, including mast cell-specific chymase and tryptase. Like macrophages and T lymphocytes, mast cells are inflammatory cells, and they participate in the pathogenesis of inflammatory diseases such as cardiovascular complications and metabolic disorders. Recent observations suggested that mast cells are involved in insulin resistance and type 2 diabetes. Data from animal models proved the direct participation of mast cells in diet-induced obesity and diabetes. Although the mechanisms by which mast cells participate in these metabolic diseases are not fully understood, established mast cell pathobiology in cardiovascular diseases and effective mast cell inhibitor medications used in pre-formed obesity and diabetes in experimental models offer hope to patients with these common chronic inflammatory diseases. This article is part of a Special Issue entitled: Mast cells in inflammation.
Topics: Adipose Tissue, White; Animals; Animals, Genetically Modified; Humans; Hypertension; Inflammation; Inflammation Mediators; Mast Cells; Metabolic Diseases; Obesity
PubMed: 21185370
DOI: 10.1016/j.bbadis.2010.12.012 -
Annals of Oncology : Official Journal... Oct 2017Clinically relevant features in patients with systemic mastocytosis (SM) include the cosmetic burden of lesional skin, mediator-related symptoms, and organ damage... (Review)
Review
Clinically relevant features in patients with systemic mastocytosis (SM) include the cosmetic burden of lesional skin, mediator-related symptoms, and organ damage resulting from mast cell (MC) infiltration in advanced forms of SM. Regardless of the SM variant, expansion of neoplastic MC in the skin and other organs is triggered by mutant forms of KIT, the most prevalent being D816V. Activation of MC with subsequent release of chemical mediators is often caused by IgE-dependent mechanisms in these patients. Midostaurin, also known as PKC412, blocks the kinase activity of wild-type KIT and KIT D816V, counteracts KIT-dependent growth of neoplastic MC, and inhibits IgE-dependent mediator secretion. Based on this activity-profile, the drug has been used for treatment of patients with advanced SM. Indeed, encouraging results have been obtained with the drug in a recent multi-center phase II trial in patients with advanced SM, with an overall response rate of 60% and a substantial decrease in the burden of neoplastic MC in various organs. Moreover, midostaurin improved the overall survival and relapse-free survival in patients with advanced SM compared with historical controls. In addition, midostaurin was found to improve mediator-related symptoms and quality of life, suggesting that the drug may also be useful in patients with indolent SM suffering from mediator-related symptoms resistant to conventional therapies or those with MC activation syndromes. Ongoing and future studies will determine the actual value of midostaurin-induced MC depletion and MC deactivation in these additional indications.
Topics: Antineoplastic Agents; Clinical Trials, Phase II as Topic; Drug Resistance, Neoplasm; Humans; Mast Cells; Mastocytosis, Systemic; Multicenter Studies as Topic; Staurosporine
PubMed: 28945834
DOI: 10.1093/annonc/mdx290 -
International Journal of Molecular... Jan 2018Historically, increased numbers of mast cells have been associated with fibrosis in numerous cardiac pathologies, implicating mast cells in the development of cardiac... (Review)
Review
Historically, increased numbers of mast cells have been associated with fibrosis in numerous cardiac pathologies, implicating mast cells in the development of cardiac fibrosis. Subsequently, several approaches have been utilised to demonstrate a causal role for mast cells in animal models of cardiac fibrosis including mast cell stabilising compounds, rodents deficient in mast cells, and inhibition of the actions of mast cell-specific proteases such as chymase and tryptase. Whilst most evidence supports a pro-fibrotic role for mast cells, there is evidence that in some settings these cells can oppose fibrosis. A major gap in our current understanding of cardiac mast cell function is identification of the stimuli that activate these cells causing them to promote a pro-fibrotic environment. This review will present the evidence linking mast cells to cardiac fibrosis, as well as discuss the major questions that remain in understanding how mast cells contribute to cardiac fibrosis.
Topics: Animals; Fibrosis; Humans; Mast Cells; Models, Biological; Myocardium
PubMed: 29329223
DOI: 10.3390/ijms19010231 -
Arteriosclerosis, Thrombosis, and... Feb 2015The mast cell is a potent immune cell known for its functions in host defense responses and diseases, such as asthma and allergies. In the past years, accumulating... (Review)
Review
The mast cell is a potent immune cell known for its functions in host defense responses and diseases, such as asthma and allergies. In the past years, accumulating evidence established the contribution of the mast cell to cardiovascular diseases as well, in particular, by its effects on atherosclerotic plaque progression and destabilization. Through its release not only of mediators, such as the mast cell-specific proteases chymase and tryptase, but also of growth factors, histamine, and chemokines, activated mast cells can have detrimental effects on its immediate surroundings in the vessel wall. This results in matrix degradation, apoptosis, and enhanced recruitment of inflammatory cells, thereby actively contributing to cardiovascular diseases. In this review, we will discuss the current knowledge on mast cell function in cardiovascular diseases and speculate on potential novel therapeutic strategies to prevent acute cardiovascular syndromes via targeting of mast cells.
Topics: Animals; Anti-Inflammatory Agents; Atherosclerosis; Drug Design; Humans; Inflammation; Inflammation Mediators; Mast Cells; Molecular Targeted Therapy; Signal Transduction
PubMed: 25104798
DOI: 10.1161/ATVBAHA.114.303570 -
European Journal of Immunology Sep 2014Mast cells regulate the immunological responses causing allergy and autoimmunity, and contribute to the tumor microenvironment through generation and secretion of a... (Review)
Review
Mast cells regulate the immunological responses causing allergy and autoimmunity, and contribute to the tumor microenvironment through generation and secretion of a broad array of preformed, granule-stored and de novo synthesized bioactive compounds. The release and production of mast cell mediators is the result of a coordinated signaling machinery, followed by the FcεRI and FcγR antigen ligation. In this review, we present the latest understanding of FcεRI and FcγR signaling, required for the canonical mast cell activation during allergic responses and anaphylaxis. We then describe the cooperation between the signaling of FcR and other recently characterized membrane-bound receptors (i.e., IL-33R and thymic stromal lymphopoietin receptor) and their role in the chronic settings, where mast cell activation is crucial for the development and the sustainment of chronic diseases, such as asthma or airway inflammation. Finally, we report how the FcR activation could be used as a therapeutic approach to treat allergic and atopic diseases by mast cell inactivation. Understanding the magnitude and the complexity of mast cell signaling is necessary to identify the mechanisms underlying the potential effector and regulatory roles of mast cells in the biology and pathology of those disease settings in which mast cells are activated.
Topics: Anaphylaxis; Animals; Humans; Mast Cells; Receptors, IgE; Receptors, IgG; Receptors, Interleukin; Signal Transduction
PubMed: 25066089
DOI: 10.1002/eji.201444546 -
Oncology Reports May 2022The role of mast cells in colorectal cancer (CRC) has been an area of intense interest. Mast cell density is closely related to CRC development and prognosis. The...
The role of mast cells in colorectal cancer (CRC) has been an area of intense interest. Mast cell density is closely related to CRC development and prognosis. The identification of mast cell progenitors (MCps) in peripheral blood provides an opportunity to explore the frequency and distribution of mast cells in the circulation and tumour microenvironment of patients with CRC at different disease stages. The aim of the presents study was to investigate the changes of MCps and mast cells in CRC. Flow cytometry was used to measure the circulating frequency of MCps in 37 patients with CRC and 12 healthy control (HC) patients, and the frequency of mast cells in tissue from 15 patients with CRC and 7 patients with haemorrhoids. In the present study, lower levels of circulating MCps in patients with CRC were found, which was significantly related to CRC development. After surgery, the frequency of circulating MCps was significantly increased. However, the frequency of mast cells in tumour tissues was lower than that in adjacent normal tissues and compared with HC tissues and was not associated with CRC progression.
Topics: Cell Count; Colorectal Neoplasms; Humans; Mast Cells; Prognosis; Stem Cells; Tumor Microenvironment
PubMed: 35293596
DOI: 10.3892/or.2022.8300 -
Cells May 2021Mast cells are unique tissue-resident immune cells of the myeloid lineage that have long been implicated in the pathogenesis of allergic and autoimmune disorders. More... (Review)
Review
Mast cells are unique tissue-resident immune cells of the myeloid lineage that have long been implicated in the pathogenesis of allergic and autoimmune disorders. More recently, mast cells have been recognized as key orchestrators of anti-tumor immunity, modulators of the cancer stroma, and have also been implicated in cancer cell intrinsic properties. As such, mast cells are an underrecognized but very promising target for cancer immunotherapy. In this review, we discuss the role of mast cells in shaping cancer and its microenvironment, the interaction between mast cells and cancer therapies, and strategies to target mast cells to improve cancer outcomes. Specifically, we address (1) decreasing cell numbers through c-KIT inhibition, (2) modulating mast cell activation and phenotype (through mast cell stabilizers, FcεR1 signaling pathway activators/inhibitors, antibodies targeting inhibitory receptors and ligands, toll like receptor agonists), and (3) altering secreted mast cell mediators and their downstream effects. Finally, we discuss the importance of translational research using patient samples to advance the field of mast cell targeting to optimally improve patient outcomes. As we aim to expand the successes of existing cancer immunotherapies, focused clinical and translational studies targeting mast cells in different cancer contexts are now warranted.
Topics: Animals; Humans; Immunotherapy; Mast Cells; Neoplasms; Toll-Like Receptors; Tumor Microenvironment
PubMed: 34063789
DOI: 10.3390/cells10061270 -
Frontiers in Immunology 2018Many mast cell-associated diseases, including allergies and asthma, have seen a strong increase in prevalence during the past decades, especially in Western(ized)... (Review)
Review
Many mast cell-associated diseases, including allergies and asthma, have seen a strong increase in prevalence during the past decades, especially in Western(ized) countries. It has been suggested that a Western diet may contribute to the prevalence and manifestation of allergies and asthma through reduced intake of dietary fiber and the subsequent production of their metabolites. Indeed, dietary fiber and its metabolites have been shown to positively influence the development of immune disorders changes in microbiota composition and the regulation of B- and T-cell activation. However, the effects of these dietary components on the activation of mast cells, key effector cells of the inflammatory response in allergies and asthma, remain poorly characterized. Due to their location in the gut and vascularized tissues, mast cells are exposed to high concentrations of dietary fiber and/or its metabolites. Here, we provide a focused overview of current findings regarding the direct effects of dietary fiber and its various metabolites on the regulation of mast cell activity and the pathophysiology of mast cell-associated diseases.
Topics: Animals; Carbohydrate Metabolism; Cell Communication; Dietary Fiber; Disease Susceptibility; Energy Metabolism; Humans; Mast Cells; Mastocytosis; Organ Specificity
PubMed: 29910798
DOI: 10.3389/fimmu.2018.01067 -
Polish Journal of Pathology : Official... 2017The inflammatory process is a complex host defence mechanism aimed at the elimination of deleterious factors disturbing homeostasis. Inflammation consists of several... (Review)
Review
The inflammatory process is a complex host defence mechanism aimed at the elimination of deleterious factors disturbing homeostasis. Inflammation consists of several interdependent stages controlled by a wide range of mediators. Those include acute phase proteins, heat shock proteins, complement components, biogenic amines, cytokines, lipid-derived mediators, reactive oxygen species, nitric oxide, proteolytic enzymes, and kinins. Due to the strategic location in the body, mast cells play a protective role in the inflammatory process, through its initiation, amplification, and resolution. Mast cells degranulate and/or newly produce, and release various mediators classified into three groups: preformed mediators, de novo synthesised lipid mediators, and newly synthesised cytokines. Those mediators have an impact on different processes occurring during inflammation, inter alia, they influence blood vessels leading to dilation, enhanced adhesion molecule expression, and increased permeability. Furthermore, mast cell mediators play a pivotal role in inflammatory cell chemotaxis, degradation of extracellular matrix proteins, impact on stationery cells and resolution of inflammation. The release of mast cell mediators and their actions constitute a highly complex and still not fully understood mechanism, which warrants further studies of the action of mast cells in inflammation. This review will focus on the current knowledge concerning the broad role of mast cells in the inflammatory process.
Topics: Animals; Humans; Inflammation; Mast Cells
PubMed: 29363910
DOI: 10.5114/pjp.2017.71526 -
The Keio Journal of Medicine Mar 1997The underlying pathophysiology of chronic urticaria is mast cell activation, with release of histamine and other mast cell mediators. A weal producing factor has been... (Review)
Review
The underlying pathophysiology of chronic urticaria is mast cell activation, with release of histamine and other mast cell mediators. A weal producing factor has been identified in the serum of 60% of patients with chronic idiopathic urticaria. In half of these patients there is evidence for functional autoantibodies against the high affinity IgE receptor or IgE, or both. These autoantibodies release histamine from basophils and mast cells. It is therefore likely that there is an autoimmune basis for up to 30% of patients with idiopathic urticaria. In the other half of patients whose serum causes weals, the factor releases histamine from mast cells only and is as yet unidentified. So far no clinical difference has been associated with presence/absence or type of weal producing factor. Exacerbating factors in chronic urticaria such as aspirin, food additives, febrile illness and psychological stress should be identified and avoided. Treatment is symptomatic with the low sedation antihistamines. In the most severe cases not responding to conventional therapy and which may have the weal producing factor, treatments with non specific immune therapy such as cyclosporin, and intravenous gammaglobulin and also plasmapheresis have been promising.
Topics: Autoantibodies; Histamine Antagonists; Histamine Release; Humans; Mast Cells; Receptors, IgE; Urticaria
PubMed: 9095581
DOI: 10.2302/kjm.46.37