Mast Cells In Allergic Inflammation Research Articles

Cysteinyl Leukotrienes and Extracellular Nucleotides Mediate the Cross-talk between Platelets and Mast cells in Allergic Inflammation

Mast cells are responsible for allergic reactions by releasing a variety of mediators such as prostaglandin D2 (PGD2) and Cysteinyl leukotrienes (CysLTs). There is accumulating evidence that platelets interact with other immune cells to boost proinflammatory responses in severe asthma and Aspirin Exacerbated Respiratory Disease (AERD). However, potential cross-talk between platelets and mast cells in allergic inflammation remains unexplored.

Histamine induced high mobility group box-1 release from vascular endothelial cells through H1 receptor.

BackgroundSystemic allergic reaction is characterized by vasodilation and vascular leakage, which causes a rapid, precipitous and sustained decrease in arterial blood pressure with a concomitant decrease of cardiac output. Histamine is a major mediator released by mast cells in allergic inflammation and response. It causes a cascade of inflammation and strongly increases vascular permeability within minutes through its four G-protein-coupled receptors (GPCRs) on endothelial cells. High mobility group box-1 (HMGB1), a nonhistone chromatin-binding nuclear protein, can be actively secreted into the extracellular space by endothelial cells. HMGB1 has been reported to exert pro-inflammatory effects on endothelial cells and to increase vascular endothelial permeability. However, the relationship between histamine and HMGB1-mediated signaling in vascular endothelial cells and the role of HMGB1 in anaphylactic-induced hypotension have never been studied.Methods and resultsEA.hy 926 cells were treated with different concentrations of histamine for the indicated periods. The results showed that histamine induced HMGB1 translocation and release from the endothelial cells in a concentration- and time-dependent manner. These effects of histamine were concentration-dependently inhibited by d-chlorpheniramine, a specific H1 receptor antagonist, but not by H2 or H3/4 receptor antagonists. Moreover, an H1-specific agonist, 2-pyridylethylamine, mimicked the effects of histamine, whereas an H2-receptor agonist, 4-methylhistamine, did not. Adrenaline and noradrenaline, which are commonly used in the clinical treatment of anaphylactic shock, also inhibited the histamine-induced HMGB1 translocation in endothelial cells. We therefore established a rat model of allergic shock by i.v. injection of compound 48/80, a potent histamine-releasing agent. The plasma HMGB1 levels in compound 48/80-injected rats were higher than those in controls. Moreover, the treatment with anti-HMGB1 antibody successfully facilitated the recovery from compound 48/80-induced hypotension.ConclusionHistamine induces HMGB1 release from vascular endothelial cells solely through H1 receptor stimulation. Anti-HMGB1 therapy may provide a novel treatment for life-threatening systemic anaphylaxis.

Role of Leukotriene B4 Receptor-2 in Mast Cells in Allergic Airway Inflammation.

Mast cells are effector cells in the immune system that play an important role in the allergic airway inflammation. Recently, it was reported that BLT2, a low-affinity leukotriene (LT) B4 receptor, plays a pivotal role in the pathogenesis of allergic airway inflammation through its action in mast cells. We observed that highly elevated expression levels of BLT2 are critical for the pathogenesis leading to allergic airway inflammation, and that if BLT2 expression is downregulated by siBLT2-mediated knockdown, allergic inflammation is dramatically alleviated. Furthermore, we demonstrated that BLT2 mediates the synthesis of vascular endothelial growth factor (VEGF) and Th2 cytokines, such as interleukin (IL)-13, in mast cells during allergic inflammation. Based on the critical roles of BLT2 in mast cells in allergic inflammation, anti-BLT2 strategies could contribute to the development of new therapies for allergic airway inflammation.

THE EFFECT OF MAGNETO-LASER THERAPY ON THE PHENOTYPE OF BASOPHILS IN CHILDREN WITH ATOPIC ASTHMA

In recent years there has been growing evidence to suggest a major role of basophils alongside eosinophils and mast cells in allergic inflammation. The aim of this study was to analyze the dynamics of the basophil phenotypes after the use of magneto-la-ser therapy in children with atopic bronchial asthma. Materials and methods. A total of 66 children with mild persistent atopic bronchial asthma (aged 6 to 18 years old) were examined. Group A included 34 children who received magneto-laser therapy together with basic asthma treatment (low dose of inhaled corticosteroids). Group B included 32 children who received only basic asthma therapy. The level of CD203с + , CD203с + CD63 + , CD203с + IgE + basophils was determined in peripheral blood in the beginning of the study, after 2 weeks and after 3 months. Results. A statistically significant decrease in the absolute levels of CD203с+CD63+ and CD203с + IgE + basophils and in the relative level of CD203с + IgE + among all CD203с + basophils was determined in group A after magneto-laser therapy. The comparison of group A and group B indices revealed a significant difference between the relative level of CD203с + IgE + basophils after 12-15 days from the beginning of the study. This indicator was significantly lower in group A than in group B (p<0.05). The absolute level of CD203с + IgE + basophils was significantly lower in group A in comparison with group B after 82-90 days (p<0.05). Conclusions. Magneto-laser therapy can change the phenotype of basophils in children with atopic bronchial asthma, causing suppression of proallergic pa-rameters. Considering these results there is reason to believe, that it is possible to use this method as an additional immunocorrective treatment in patients with basophilic phenotype of atopic asthma.

THE EFFECT OF MAGNETO-LASER THERAPY ON THE PHENOTYPE OF BASOPHILS IN CHILDREN WITH ATOPIC ASTHMA

In recent years there has been growing evidence to suggest a major role of basophils alongside eosinophils and mast cells in allergic inflammation. The aim of this study was to analyze the dynamics of the basophil phenotypes after the use of magneto-la-ser therapy in children with atopic bronchial asthma. Materials and methods. A total of 66 children with mild persistent atopic bronchial asthma (aged 6 to 18 years old) were examined. Group A included 34 children who received magneto-laser therapy together with basic asthma treatment (low dose of inhaled corticosteroids). Group B included 32 children who received only basic asthma therapy. The level of CD203с + , CD203с + CD63 + , CD203с + IgE + basophils was determined in peripheral blood in the beginning of the study, after 2 weeks and after 3 months. Results. A statistically significant decrease in the absolute levels of CD203с+CD63+ and CD203с + IgE + basophils and in the relative level of CD203с + IgE + among all CD203с + basophils was determined in group A after magneto-laser therapy. The comparison of group A and group B indices revealed a significant difference between the relative level of CD203с + IgE + basophils after 12-15 days from the beginning of the study. This indicator was significantly lower in group A than in group B (p<0.05). The absolute level of CD203с + IgE + basophils was significantly lower in group A in comparison with group B after 82-90 days (p<0.05). Conclusions. Magneto-laser therapy can change the phenotype of basophils in children with atopic bronchial asthma, causing suppression of proallergic pa-rameters. Considering these results there is reason to believe, that it is possible to use this method as an additional immunocorrective treatment in patients with basophilic phenotype of atopic asthma.

The roles of mast cells in allergic inflammation and mast cell-related disorders

Mast cells, which are major effector cells in allergic reactions, are found in the perivascular spaces of most tissues and contain pro-in-flammatory and vasoactive mediators. These mediators are released after IgE receptor cross-linking induced by allergens or other stimuli, including anaphylatoxins (C3a and C5a), aggregated IgG, certain drugs, venoms, and physical stimuli (pressure and tempera-ture changes), as well as cytokines and neuropeptides. The excess release of these mediators can cause variable allergic symptoms and signs, such as bronchospasm, itching, flushing, nausea, vomiting, diarrhea, abdominal pain, vascular instability, and anaphylaxis. Furthermore, mast cell disorders may involve either excessive proliferation of mast cells or abnormal mast cell reactivity. Mast cell disorders can be broadly divided into 3 types: primary, secondary, and idiopathic. All of these disorders present with signs and symp-toms of mast cell activation and differ in severity and involvement of various organ systems. The best characterized primary disorder is mastocytosis. Systemic and cutaneous forms of the disease are well described. Secondary disorders include typical allergic dis-eases and some types of urticarial diseases. In this article, the biochemical characteristics of mast cells and the role of mast cells in al-lergic inflammation, as well as the classification, diagnosis, and management of mast cell-related disorders, will be reviewed. (Allergy Asthma Respir Dis 2017;5:248-255)

Association between perfluorooctanoic acid exposure and degranulation of mast cells in allergic inflammation.

Perfluorooctanoic acid (PFOA) has wide applications, including as a raw material for converted paper and packaging products. With the widespread use of PFOA, concerns regarding its potential environmental and health impacts have increased. In spite of the known hepatotoxicity and genotoxicity of PFOA, correlation with PFOA and allergic inflammation is not well known. In this study, the effect of PFOA on the degranulation of mast cells and mast cell-mediated allergic inflammation in the presence of FcεRI cross-linking was evaluated. In immunoglobulin (Ig) E-stimulated mast cells, PFOA increased the release of histamine and β-hexosaminidase by the up-regulation of intracellular calcium levels. PFOA enhanced gene expression of several pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 by the activation of nuclear factor (NF)-κB in IgE-stimulated mast cells. Also, PFOA exacerbated allergic symptoms via hypothermia, and an increase of serum histamine, TNF-α, IgE and IgG1 in the ovalbumin-induced systemic anaphylaxis. The present data indicate that PFOA aggravated FcɛRI-mediated mast cell degranulation and allergic symptoms. Copyright © 2016 John Wiley & Sons, Ltd.

Progress in Allergy Signal Research on Mast Cells: Systemic Approach to Mast Cell Biology in Allergic Diseases

At the end of the last century, microarray technology that examines the total genes and transcripts present in a cell became available as a laboratory tool. Mast cells are known to play a pivotal role in initiating allergic inflammation by releasing various mediators and cytokines. According to the recent microarray-based studies, mast cells have been found to be much more versatile functional molecules than we ever thought. Also, genes that are exclusively expressed in mast cells have been identified in comparison with other cell types. In this article, the outcome of microarray-based analyses on the role of mast cells in allergic inflammation will be reviewed by focusing on the mast cell–specific genes as drug targets.

Human peripheral blood eosinophils express stem cell factor

AbstractStem cell factor (SCF) or c-Kit ligand is a cytokine associated with the differentiation, survival, and activation of mast cells. Eosinophils have pleiotropic functions in several diseases and, together with mast cells, are key cells in allergy. Mast cell–eosinophil interactions can take place during the late and chronic phases of allergy. It was, therefore, investigated whether eosinophils can produce SCF and consequently influence mast cells. Human peripheral blood eosinophils variably expressed mRNA for the soluble and uncleaved forms of SCF (reverse transcription–polymerase chain reaction) and produced the 18.5-kd protein backbone of SCF (Western blot analysis). After overnight incubation in medium, eosinophils also produced SCF of higher molecular weight (42-45 kd) that might represent its glycosylated forms. Eosinophils expressed cytoplasmic SCF that colocalized with major basic protein (confocal laser microscopy). Freshly isolated eosinophils contained 8.9 ± 1.7 pg SCF/106 (mean ± SEM; enzyme-linked immunosorbent assay). Although overnight incubation of the eosinophils in either culture medium or in phorbol 12-myristate 13-acetate–calcium ionophore did not cause the secretion of SCF, the addition of chymase induced SCF release. In summary, it was demonstrated that human peripheral blood eosinophils are a source of SCF. These results may contribute to a better understanding of the interactions between eosinophils and mast cells in allergic inflammation.

Revisiting the roles of mast cells in allergic rhinitis and its relation to local IgE synthesis.

Mast cells are important effector cells in the immediate-phase allergic reaction. However, in recent years much evidence has accumulated on the versatile role of mast cells in allergic inflammation. The present article is an overview of the roles of mast cells in allergic inflammation, especially in light of the local production of IgE and the IgE-IgE receptor network. Although both nasal mast cells (NMC) and T cells in allergic rhinitics are important sources of Th2-type cytokines like IL-4 and IL-13, and can induce IgE synthesis, we report here that antigen-activated NMC can secrete greater levels of IL-4/IL-13 and induce increased levels of IgE synthesis than antigen-activated nasal T cells. Furthermore, IgE production can occur locally in the nasal mucosa (target organ) and IgE itself can enhance the Fc epsilon RI expression and subsequent mediator release from NMC, thus contributing to the perpetuation of on-going allergic inflammation. Again, mast cells can contribute to the late-phase allergic reaction not only via the upregulation of adhesion molecules like VCAM-1, but also through the interactions of NMC with the extracellular matrix proteins, and interaction of NMC with nasal epithelial cells (NEC). Thus, it is increasingly evident that mast cells are not only important for the genesis of the allergic reaction, but also contribute to the late-phase allergic reaction and on-going allergic inflammation.

Stem cell factor mRNA expression and production in human nasal epithelial cells: Contribution to the accumulation of mast cells in the nasal epithelium of allergy

Background: In allergic rhinitis, mast cells are increased in number in the epithelium of the nasal mucosa and play an important role in the immediate response. However, the mechanism of the accumulation is not known. Objective: The purpose of this study was to determine whether the nasal epithelial cells produce stem cell factor (SCF), the mast cell growth and chemoattractant factor, and contribute mast cell hyperplasia in the epithelium of allergic rhinitis. Methods: We have characterized the cellular localization of SCF using immunohistochemistry, reverse transcribed–PCR, and ELISA; compared SCF production of cultured epithelial cells between patients with allergic rhinitis and nonallergic subjects; and compared the SCF production with the number of mast cells and the histamine content in the nasal epithelial scrapings. Results: Immunohistochemically, SCF was identified in the nasal epithelium of the biopsy specimens and in cultured nasal epithelial cells. SCF mRNA was expressed by cultured nasal epithelial cells not only in patients with allergy but also in subjects with no allergy. However, the SCF/β-actin mRNA ratio and SCF production in day 7 cultured epithelial cells was significantly higher in allergic than in nonallergic subjects ( P = .0424, P = .0085, respectively). SCF production from nasal scrapings in culture was strongly correlated with the number of mast cells ( r = 0.506, P = .0023) and the histamine content ( r = 0.480, P = .0040). Conclusions: These findings demonstrate that nasal epithelial cells produce SCF and may be important in the attraction, proliferation, and activation of mast cells in allergic inflammation in the nose. (J Allergy Clin Immunol 1998;102:757-64.)

Mast cells in clinical dermatology

Recent advances in cutaneous mast cell biology are briefly reviewed with special reference to our own studies on cultured human mast cells. Of note are the heterogeneity of mastocytosis, the important participation of mast cells in allergic inflammation by releasing cytokines and the inhibitory effect of histamine release from mast cells by phototherapy. It is also stressed that mast cells play a major role in tissue remodelling. These novel findings suggest that mast cells can no longer be regarded simply as cells that initiate immediate allergic reactions, but that they are responsible for various chronic inflammatory or immunological events through cytokine-dependent leucocyte recruitment. The regulation of mast cell activation should be a critical issue and, thus, a promising therapeutic approach in clinical dermatology.

New roles of mast cells in allergic inflammation

Mast cells have been recognized as one of the most important effector cells in IgE-dependent allergic reactions. Recently, the relationship between mast cells and fibroblasts has been indicated in the process of fibrotic conditions. Actually the number of mast cells is increased in the specimens obtained from fibrotic diseases, such as the involved skin of keloid and the forearm in an early stage of systemic sclerosis. Our studies showed that activation of human mast cells, which were generated from cord blood in the presence of stem cell factor and interleukin 6, increased [3H] thymidine incorporation into human fibroblasts, indicating that the mast cells possess a proliferating activity on fibroblasts. Tryptase has been indicated as one of the fibrogenic factors. In addition, our studies showed that cord blood-derived human cultured mast cells constitutively express mRNA for transforming growth factor β1, which can be involved in fibrotic conditions. These data indicate that mast cell is now being recognized to play new roles in allergic inflammation.

Biological functions of serine proteases in mast cells in allergic inflammation

Serine proteases in mast cell granules, such as chymase, atypical chymase, and tryptase, which are major proteins in the granules, may play important roles in the process of immunoglobulin E (IgE)-mediated degranulation and in pathobiological alterations in tissues. Indeed, inhibitors of chymase, substrate analogs, and antichymase F(ab')2, but not inhibitors of tryptase, markedly inhibited histamine release induced by IgE-receptor bridging but not that induced by Ca ionophore. In contrast, inhibitors of metalloprotease inhibited histamine release induced not only by IgE-receptor bridging but also by Ca ionophore. These results suggest that chymase and metalloprotease are involved at different steps in the process of degranulation. The extents of inhibition of histamine release were closely correlated with the amounts of the inhibitors of chymase accumulated in the granules. After degranulation, the released proteases may in part contribute to pathobiological alterations in allergic disorders through generations of C3a anaphylatoxin and thrombin by human and rat tryptase, respectively, and those of angiotensin II and a chemotactic factor of neutrophils by human and rat chymase, respectively. Moreover, chymase and atypical chymase from rat were shown to destroy type IV collagen, and human tryptase was found to hydrolyze various plasma proteins, such as fibrinogen and high-molecular-weight kininogen. The biological activities of tryptase and chymase from rat may be regulated by their dissociation from and association with trypstatin, an endogenous inhibitor of these proteases.

Eosinophil, basophil leukocytes and mast cells in allergic inflammation

Recent advances in the study of eosinophils, basophil leukocytes and mast cells in allergic inflammation of the airway are summarized, including their chemotaxis, mediator release and function.Different kinds of chemotactic factors for eosinophil leukocytes are reported. Of them, ECF-A may be the most important in specifity, intensity and the amount released in allergic lesion. On the other hand the chemotactic factor for basophil leukocyte is still not at all understood.Both eosinophil, basophil leukocytes and mast cells are degranulated and release extracelluraly different kinds of inflammatory mediators as sequences of allergic reaction.From basophil leukocytes and mast cells, mediators such as histamine, proteoglycan, proteases, hydrolytic enzymes, oxydative enzymes, kinin, eosinophil chemotactic factor, leukotrien C4 and B4, thromboxane A2 and prostaglandin et al. are released; and from eosinophil leukocytes, mediators such as neutral proteases, hydrolytic enzymes, oxidative enzymes, major basic protein, eosinophil cationic protein, eosinophil derived neurotoxin, Charcot Leyden Crystal, leukotrien C4, prostaglandin E1 and E2, platelet activating factor et al. are released.These mediators produce various pathological conditions, that is, contraction of the smooth muscles, increased permeability of the blood vessels, hypersecretion from the secretory glands, migration of the white cells, and irritation to the nerves. In allergic rhinitis, histamine and leukotrien may play the most important role in these inflammatory processes.