Mast cells have long been recognized as the critical tissue-based effector cells in IgE-mediated allergic diseases. Ligation of the high-affinity receptor for IgE (FceRI), constitutively expressed on mast cells, promotes cell activation and immediate release and production of pro-inflammatory mediators. Besides these positive signals, FceRI aggregation has recently been understood to generate negative intracellular signals capable of limiting mast-cell functional responses. This review is aimed at providing a summary of the mechanisms through which FceRI engagement can generate negative signals and regulate mast-cell function. Similar mechanisms are employed by other receptors expressed by immune cells, such as T cell and B cell receptors, pointing to a general concept in negative immunoreceptor signaling.
Mast cells are important effector cells in allergic inflammatory reactions. The aggregation of the high-affinity IgE receptor (Fc epsilon RI) on the surface of mast cells initiates a complex cascade of signaling events that ultimately leads to the release of various mediators involved in allergic inflammation and anaphylactic reactions. The release of these mediators is tightly controlled by signaling pathways that are propagated through the cell by specific phosphorylation and dephosphorylation events. These events are controlled by protein kinases and protein phosphatases which either positively or negatively regulate the propagation of the signal through the cell. This review summarizes the role of both positive and negative regulators of Fc?RI-induced mast cell activation.
The study was undertaken to examine the effect of isoprinosine treatment on in vitro histamine release from peritoneal mast cells. The experiments were done on mice which received isoprinosine orally, at a dose of 50 or 100 mg per kilogram of body weight per day, in divided doses, every 8 hours, for a period of 1 - 9 days. After isoprinosine treatment, there was a significant decrease of in vitro Con A-induced histamine release from mast cells. This inhibitory effect was observed in both tested groups. In the second experiment, with mice sensitized with egg albumin, the treatment with isoprinosine gave also a significant inhibition of anaphylactic histamine release from mast cells, as compared with that of control without isoprinosine treatment. Results of both experiments suggested that isoprinosine may have some inhibitory effect on mast cell activation.
Human mast cells were obtained from adenoids and mesentery by enzymatic dispersion of the tissues with the enzyme collagenase. The digestion of the tissues resulted in a cell suspension which contained 1 - 2% mast cells. 37,3% (adenoids) and 33,4% (mesentery) of total histamine initially present in the tissues was recovered in the dispersed cell suspensions. More than 90% of the cells were viable. The adenoidal mast cells could be sensitized passively in vitro with homologous reaginic serum and released histamine after challenge with specific antigen. Both populations of mast cells were sensitive to the action of anti-human IgE: the reversed anaphylaxis with anti-IgE was higher in mesenteric mast cells. Both examined mast cell populations were sensitive to the challenge with polymyxin B, concanavalin A and ionophore A23187, however, histamine release was only up to 10% and 20% for adenoidal and mesenteric cells, respectively. Only mesenteric mast cells responded to the action of compound 48/80. Histamine release induced by polymyxin B, was rapid (maximal release within 5 min), maximal in the presence of 3 mM extracellular calcium ions (but also occured in the absence of the cation).
The purpose of the present study was: (1) to demonstrate immunocytochemically the localization of histamine in the wall of four chicken oviductal parts, i. e. infundibulum, magnum, isthmus, and shell gland, (2) to identify the presence of mast cells in chicken oviduct, and (3) to determine histamine concentration in oviductal tissue by the spectrofluorometric method. Experiments were carried out on Isa Brown laying hens decapitated just after oviposition. The specific immuno-reactivity for histamine and the presence of mast cells were found in the wall of all the examined oviductal parts. The immuno-reactive histamine was localized in epithelium, tubular glands, connective tissue layer, circular and longitudinal muscles, and endothelium and muscles of blood vessels. The intensity of immuno-positive reaction was as follows: infundibulum > shell gland > magnum = isthmus and correlated with quantitatively determined histamine level and tissue density of mast cells. It is suggested that mast cells are the main source of histamine in the chicken oviduct.
Urticaria is a relatively common autoimmune/autoreactive skin disorder that may severely impair quality of life. Although rarely life-threatening, widespread urticaria and its associated angioedema can be an extremely disabling and difficult-to-treat condition. Patients may suffer symptoms such as pruritus and disfigurement due to wheals for years or decades. Urticaria is caused by cutaneous mast-cell degranulation attributed to immunological, non-immunological, and idiopathic causes. The last decade has seen some notable advances in the understanding of the etiology and pathogenesis of common forms of urticaria and their management. Furthermore, the wide diversity in urticaria subtypes has been identified and this reflects a partial understanding of the causes or factors that trigger it as well as the molecular and cellular mechanisms that are involved in its physiopathology. In addition, new instruments for diagnosing urticaria variants and for assessing quality of life in urticaria patients have been developed. Finally, several clinical trials have demonstrated the efficacy of novel treatment approaches for urticaria, while other therapeutic concepts are under development. The objective of this article was to review the literature to be able to offer the readers comprehensive and updated information on the basic etiological and physiopathological mechanisms and to make special emphasis on the current management of urticaria, thus promoting continuous medical education.
In the course of hemorrhagic shock. Here are multidirectional organ changes that result in intensified disjunction of important organs as well as multiorgan insufficiency syndrome. The syndrome is a cause of high post-traumatic mortality. The general inflammatory reaction of intensive ? liver ? lungs ? immunological system increases in a cascadical way and has a significant role in the pathogenesis of the syndrome. Most cells activated as a result of ischemia and reprefusion participate in the phenomenon.
It is well documented that most if not all aspects of mast cell development, including growth, proliferation, and the differentiation/maturation are regulated by cytokines. Nowadays there is growing evidence that cytokines also influence the biology and function of mature tissue mast cells. Some cytokines activate mast cells directly to mediator release or modulate their reactivity to other stimulating agents. Various cytokines affect mast cells migration and expression of cell receptors, at the same time regulating the survival of tissue mast cells. Taking into account that mast cells themselves are the source of many cytokines (both preformed and newly generated) it can be assumed that these cytokines regulate the function of mast cells in tissues in autocrine manner
Mast cells have long since been recognized as potent producers of a large panel of biological highly active mediators such as biogenic amines, arachidonic acid metabolites, cytokines and chemokines, but most of their biological functions had been elusive and speculative. By taking advantage of mast cell-deficient mice, the role of mast cells in a variety of experimental settings can now be studied in detail and such approaches have dramatically altered and enlarged our knowledge about mast cell biology and function. Herein we will focus on the role of mast cells in inflammatory reactions of diverse origin such as delayed type hypersensitivity, atopy, immune complex-mediated inflammation and innate immune responses. From a current point of view, there is no doubt that the most outstanding and beneficial feature of mast cells is their recently uncovered ability to rapidly induce a life-saving inflammatory response upon encountering microbes and microbial constituents. Nevertheless, the picture is also emerging that mast cells are deeply involved in the induction and maintenance of a variety of severe allergic and autoimmune diseases. However, a deeper understanding of their activation and immune-modulatory capacity might open a new window for the development of curative strategies.
The pine caterpillar Thaumetopoea pityocampa (Lepidoptera: Thaumetopoeidae) is found in pine woods. Hairs of the T. pityocampa caterpillar cause a cutaneous reaction in humans and animals. Mast cells are responsible for allergic reactions in mammals. In this study male swiss albino mice were divided into two groups: 5 mice in the control group and 25 mice in the experimental group. The dorsal skin of mice was shaved. The mice in the experimental group and T. pityocampa larvae (fifth instar, approximately n=100) were put in the same cage. Dermal mast cells of mice exposed to T. pityocampa were examined with a transmission electron microscope and compared to the control group 1, 3, 6, 12 and 24 hours after exposure. Dermal mast cell degranulation in mice was observed 12 and 24 hours after exposure.
Mast cells (MC) are found widely distributed in tissues and contribute to regulation of inflammatory responses and ongoing modulation of the tissues. Although MC are important in a variety of processes including innate immunity, their role in allergic disease has received increasing attention in the past decade. MC are located throughout the human body and upon allergen exposure they are stimulated via the IgE receptor (FceRI) to release several proinflammatory mediators such as tumor necrosis factor (TNF), reactive oxygen species such as nitric oxide (NO), proteases, and lipid-derived mediators. However, we now recognize that MC can be activated by a variety of mechanisms and that mediator release is a consequence of several intra- and extracellular signals. Some of these mechanisms, such as Fc receptor aggregation and proteinase activated receptor (PAR)-mediated activation facilitate and augment local inflammatory responses. Other mechanisms, such as interferon gamma (IFN-gamma) induction of nitric oxide (NO) may inhibit MC function and downregulate inflammatory responses. Increased understanding of these complex pathways has encouraged the development of therapies for allergic inflammation that target specific MC functions and mediators. Some novel strategies include oligonucleotides that induce or inhibit the production of specific mediators. Such approaches may yield useful therapies for allergic individuals in the near future.
Mast cells play a critical role in allergic diseases. When mast cells are activated by cross-linking of their high affinity IgE receptors by the antigen and IgE antibodies, release of chemical mediators is followed by secretion of multiple cytokines. We report that IL-3-dependent mucosal-type mast cells undergo apoptosis when IL-3 is withdrawn. In addition, cross-linking of high affinityIgE receptors prevents apoptosis of mast cells by paractine mechanisms, producing IL-3, IL-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF). However, the secretion of endogenous growth factors are not enough for cell survival, whereas IL-4 induces cell aggregation by expressing adhesion molecules such as leukocyte function-associated antigen 1 (LFA-1), and makes it reactive to endogenous growth factors by contact cell to cell interaction. On the other hand, dexamethazone down-regulates the expression of intracellular adhesion molecule 1 (ICAM-1) and IL-4 in activated mast cells, by which the self-aggregation of mast cells is inhibited and poptosis is induced. Thus, glucocorticoids suppress mast cell survival by inhibiting IL-4 production and expression of adhesion molecules.
Specimens of mouse mammary glands obtained from animals being in different phases of reproductive cycle were collected. After staining MCN, the total mast cell area (TMC), mean mast cell area (MMC), and lactiferous structure density index (LDI) were examined in sections, using a computer image analysis system. Statistically significant (P<0.05) results were: 1. An increase in MCN observed in Group I (4-5 and 9-10 days of pregnancy), a decrease in MCN observed in Group II (2nd and 10th day of lactation); 2. Changes of TMC fully corresponding to changes of MCN; 3. Increase in MMC observed in Group I at mid (days 9-10) and at the end (days 18-19) of pregnancy, decrease in MMC observed in Group IIB (10th day of lactation); 4. LDI (%) higher at the end of pregnancy (Group IC) and during lactation (groups IIA, IIB), compared with control (23.5 ? 4.12, 37.6 ? 3.24, 71.0 ? 4.33 vs. 3.8 ? 0.39). The observed changes in the number and size of MC strictly correspond to physiological phenomena leading to alternation of the mouse mammary gland functional status by development/involution of the lactiferous structures.
Mast cells (MCs) are both central effectors and signaling cells in allergic reactions. Their key role in the immunopathology of asthma and other allergic diseases has been well documented. Molecular events leading to MC activation have not been yet fully established, however. Recent studies emphasize the key role of the protein tyrosine kinases Lyn and Fyn in MC signal transduction. The finding that Lyn kinase negatively regulates MC degranulation and that Fyn kinase enhances this effector response is of great importance. This creates new possibilities for therapeutic intervention in asthma and other allergic diseases. This review summarizes current knowledge on MC intracellular signaling and discusses the most recent strategies for the treatment of allergic diseases based on MC signaling pathway inhibition.
Tissue mast cells are multifunctional immune cells and have been implicated in allergic and inflammatory reactions. They used to be regarded merely as a source of histamin, prostaglandins and leukotriens which mediated the symptoms of the acute allergic reaction but more recent work has indicated they are involved in many inflammatory reactions. The discavory of production and secretion of a unique array of cytokines by these cells has suggested new ways in which they could influence to the development of inflammation. Many experiments have disclosed that mast cells owning to cytokines can not only initiate but also regulate and modulate this process. With the results come the realisation that these cytokines might represent important effector molecules in a variety of pathologic and physiologic processes where mast cells involvment had been postulated but an understanding of the mechanisms remained obscure. The aim of this article is introduction the biology of mast cells and presentation the information concern production and secretion of cytokines by these cells like also influence of these biologically active molecules on inflammatory process.
The head kidney morphology of the goldfish with the experimental peritoneal inflammation (on day 2 after i.p. injection with sterile 3% Thioglycollate) is compared with that in the control fish (i.e. on day 2 after i.p. injection with a strile physiological saline PBS) with special emphasis on identification of granulocytes on semithin and consecutive ultrathin sections. The most striking feature of head kidneys of goldfish in the course of peritoneal inflammation is a severe depletion of mature neutrophils and cells with basophilic granules (basophils/mast cells). These observations suggest the involvement of the head kidney, the main hematopoietic organ of teleosts, in the inflammatory process.
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.