Identification Of Mast Cells Research Articles

Optimization of the Method for the Identification of Mast Cells Using Cresyl Violet

Optimization of the Method for the Identification of Mast Cells Using Cresyl Violet

Evaluation of bronchoalveolar lavage fluid from donkeys using four different cytological stains: A pilot study

Bronchoalveolar lavage fluid (BALF) cytology is used for the diagnosis of non-infectious lower airway inflammation in equids. Discrepancies have been reported in the differential cell count when different staining methods were used both in humans and horses. The objective of this study was to compare the results of BALF cytology in donkeys using four different staining methods: modified May-Grunwald Giemsa (mMGG), Diff-Quick (DQ), Toluidine blue (TB) and Perls Prussian blue (PPB). Nine healthy Amiata female donkeys were enrolled. The BAL procedure was performed as previously described and pairs of cytocentrifuged BALF slides were stained with each method. No differences between mMGG and DQ were found for macrophages, neutrophils, and eosinophils, while differences were found in mast cell count between DQ vs.TB, but not between mMGG vs. DQ or mMGG vs. TB. Finally, no differences were obtained in the differential count for hemosiderophages comparing mMGG, DQ and PPB. The mMGG appears to be an excellent stain for the identification of all possible cell types, including mast cells in the BALF of donkeys. DQ, if used alone, may lead to inappropriate identification of mast cells. These results are consistent with the literature on BALF staining methods in horses.

TUMOR MICROENVIRONMENT-ASSOCIATED miR-7-5p, miR-19a-3p, AND miR-23b-3p EXPRESSION IN PROSTATE CANCER WITH DIFFERENT PROGRESSION RISK.

The tumor microenvironment (TME) plays an important role in the occurrence and progression of prostate cancer (PCa). At the same time, the mechanisms and features of the interaction between tumor cells and individual components of the TME in PCa remain not fully elucidated. The aim was to study the expression levels of tumor-associated miR-7-5p, miR-19a-3p, and miR-23b-3p in the PCa tissue and to analyze their relationship with the features of TME. The work is based on the analysis of the results of the examination and treatment of 50 patients with PCa of stages II-IV. The expression of miRNA in the PCa tissue was analyzed by the real-time polymerase chain reaction. The expression of alpha-smooth muscle actin (α-SMA), vimentin (VIM), and CD68 in PCa tissue was determined by the immunohistochemical method. The identification of mast cells in the PCa tissue was assessed by the histochemical method. The analysis of the expression levels of tumor-associated miRNAs demonstrated that the tumor tissue of patients with a high risk of PCa progression was characterized by 4.93 (p < 0.01) and 8.97 (p < 0.05) times higher levels of miR-19a-3p and miR-23b-3p, respectively, compared to similar indicators in the group of patients with a low risk of PCa progression. The levels of miR-7-5p and miR-19a-3p expression in the PCa tissue correlated with the expression level of α-SMA (r = 0.49 and r = 0.45, respectively; p < 0.05) and VIM (r = 0.45 and r = 0.46; respectively, p < 0.05). A direct relationship (r = 0.44; p < 0.05) was established between the level of miR-7-5p expression and the degree of infiltration of the prostate gland tissue by tumor-associated macrophages. The features of the expression of tumor-associated miR-7-5p, miR-19a-3p, and miR-23b-3p indicated the prospect of their use as markers of the aggressiveness of the PCa course.

Identification of mast cells in the brain of mice with lipopolysaccharide-induced neuroinflammation

The purpose of the present study was to identify mast cells in brain sections of mice with neuroinflammation induced by intraperitoneal injections of LPS. Material and methods. The subjects of the study were nonlinear mice that received intraperitoneal injections of LPS at a dose of 1 mg/kg or sterile 0.9% NaCl. Serial frontal sections of the brain were prepared using a cryostat. To identify mast cells, sections were stained with brilliant green and methylene blue. Results. The findings suggest that intraperitoneal administration of LPS increases the number of resident mast cells in the mouse brain, especially in the perivascular areas between the hippocampus and thalamus. The increase in the number of cells appears to be the result of their division or directed migration under conditions of developing inflammation. Conclusion. Administration of LPS leads to an increase in the number of mast cells in the brain of mice. Mast cells are likely to be an important source of immune mediators in LPS-induced neuroinflammation, as evidenced by their active degranulation process.

Identification of Mast Cells and Immunophenotypic Subtypes in Peripheral Nerve Damage Caused by Epineurotomy and Systemic Inflammation

ABSTRACT Purpose: This study aims to investigate the numerical increase, localization, granulation status, and immunophenotypic properties of mast cells (MCs) in epineurectomy-induced nerve damage and lipopolysaccharide (LPS)-induced systemic infection models. Materials and Methods: In this study, the animals were divided into three groups of 6 each. One of the groups was determined as the control group, epineurectomy was applied to one group, and systemic inflammation was created by regular LPS injections in the other group. Then, the obtained nerve tissues were stained histochemically with Hematoxylin and Eosin toluidine blue, and the increase, localization, and granulation status of MCs were examined. Immunohistochemically, antitryptase and antichymase staining were performed to determine the immunophenotypes of MCs. Results: As a result, while the number of MCs increased in both groups compared to the control group, MCs in the LPS group were in the epineurium, and MCs in the epineurotomy group were located between the nerve fibers. While MCs in the LPS group showed very severe degranulation, mild degranulation was observed in the epineurotomy group, and almost no degranulated MCs were observed in the control group. Conclusion: This study is critical because it is one of the first studies to compare MCs in different nerve damage types and examine the expression of chymase and tryptase.

A Double Histochemical/Immunohistochemical Staining for the Identification of Canine Mast Cells in Light Microscopy.

Immunohistochemistry (IHC) is a widely used technique in diagnostic pathology, but the simultaneous analysis of more than one antibody at a time with different chromogens is rather complex, time-consuming, and quite expensive. In order to facilitate the identification of mast cells (MCs) during immunohistochemical analysis of membrane and/or nuclear markers, we propose a new staining method that includes the association of IHC and toluidine blue as a counterstain. To achieve this goal, we tested c-kit, Ki67, and cannabinoid receptor 2 on several cases of cutaneous canine mast cell tumors (MCTs), cutaneous mastocytosis, and atopic dermatitis. The results obtained show how this double staining technique, although limited to non-cytoplasmic markers and of little use in poorly differentiated MCTs in which MC metachromasia is hard to see, can be used during the evaluation of nuclear and/or membranous immunohistochemical markers in all canine cutaneous disorders, especially if characterized by the presence of a low number of MCs. It can help to evaluate those MCTs in which neoplastic MCs must be clearly distinguished from inflammatory cells that can infiltrate the tumor itself, in facilitating the calculation of the Ki67 index. Moreover, it can be used to study the expression of new markers in both animal and human tissues containing MCs and in MC disorders.

Relevance of mast cell infiltration in well-differentiated oral squamous cell carcinoma in biopsy specimen

Oral cancer is very common worldwide. More than 90% of all oral cancers are squamous cell carcinoma (SCC). The molecular biological markers of oral SCC have been extensively studied to aid in prevention and prognosis. However, no marker has been universally accepted so far. Mast cells are important component of cancer stromal interaction. Their early recruitment in tumor microenvironment and multifarious function make them a burning topic of interest in the field of research. So mast cell may act as a new target for the adjuvant treatment of oral SCC. Therefore, the aim of the study was to assess the number of mast cell infiltrations in well differentiated oral SCC. In this cross-sectional study the sample size was 66. After routine tissue processing and staining with Hematoxylin &amp; Eosin (H/E) stains slides of all cases were grouped as well differentiated oral SCC. Identification of mast cell was done by Toluidine blue stain. Distribution of mast cells was observed and number of mast cells was counted. The data was tabulated and statistical analysis was performed. The number of mast cell was highly increased in all cases of oral SCC than normal. The mean ± SD number of mast cells was 3.28 ± 1.21 in oral SCC, whereas in control oral tissue it was 0.44 ± 0.19. The p-value was found to be highly significant (p&lt;0.001). So, in our observation mast cell is a good cellular indicator of tumorigenesis. Mediscope 2021;8(2): 67-74

A Survey of Methodologies for Assessing Mast Cell Density and Activation in Patients with Functional Abdominal Pain Disorders

The aim was to assess methods utilized in assessing mast cell involvement in functional abdominal pain disorders (FAPDs), specifically to describe variability in methods utilized to assess both mast cell density and activation and determine if a consensus exists. After a literature search identified 70 manuscripts assessing mast cell density, data were extracted including FAPD diagnosis, site of biopsy, selection of microscopic fields analyzed, selection of mucosal region analyzed, method of mast cell identification, method to assess mast cell density, and if performed, method to assess mast cell activation. There appears to be some consensus favoring inmmunohistochemical stains over histochemical stains for identifying mast cells. Otherwise, considerable variability exists in methodology for assessing mast cell density and activation. Regardless of method, approximately 80% of studies found increased mast cell density and/or activation in comparison to controls with no method being superior. A wide variety of methods have been employed to assess mast cell density and activation with no well-established consensus and inadequate data to recommend specific approaches. The current methodology providing physiologic information needs to be translated to a standard methodology providing clinical information with the development of criteria establishing abnormal density and/or activation, and more importantly, predicting treatment response.

Identification of mast cells as a candidate significant target of immunotherapy for acute myeloid leukemia

ABSTRACT Objection Immunotherapy based on T cells is a new therapy for Acute myeloid leukemia (AML). However, there has not been considerable improvement compared with traditional chemotherapeutics. This study aimed to identify important immune cells, genes, and drugs associated with the immunotherapy of AML. Methods The gene expression profile and clinical data of patients with AML were downloaded from TCGA database, and the abundance ratio of immune cells was obtained via CIBERSORT. Kaplan–Meier (KM) survival analysis was used to assess the relationship between immune cells and survival time of patients with AML. Differentially expressed genes (DEGs) analysis was conducted to obtained DEGs related to mast cells. Then, protein-protein interaction (PPI) analysis and enrichment analysis were performed to explore the hub genes. Finally, Connectivity Map (CMap) database was utilized to predicts potential drugs that may reverse or induce the mast cell-related gene expression. Results Our study showed that mast cell was correlated with survival time of patients with AML, and 135 genes were screened to be related with mast cells. 6 hub genes were identified via PPI network, and 3 potential small molecule drugs were screened to be related to regulating the mast cell-related gene expression via CMap database. Conclusion The hub genes and drugs have high research value and clinical application in AML therapy. Our study not only provides gene targets and small molecule drugs for AML immunotherapy concerning mast cells but also provides new ideas for researchers to explore immunotherapy targets of other tumors.

Significance of Mast Cells in Uterine Cervical Lesions: A Cross-sectional Study

Introduction: Cervical cancer is the leading cancer in Indian women. Mast cell distribution and density support a diagnosis in addition to routine histopathological examination. Aim: To study the variation of mast cell distribution and density in different uterine cervical lesions. Materials and Methods: A total of 352 cases of cervical lesions were studied cross-sectionally from June 2018 to May 2020, in the Department of Pathology, Subharti Medical College, and associated Chhatrapati Shivaji Hospital, Meerut, Uttar Pradesh, India. These included both hysterectomy (296 cases) and cervical (56 cases) biopsies. Routine histopathological examination was done with Haematoxylin and Eosin stain (H&amp;E) to categorise the lesions into non-neoplastic and Neoplastic lesions. For identification of mast cells 1% toluidine blue stain was applied to evaluate mast cell distribution and density. Data analysis was done using analysis of variance (ANOVA): one-way t-test was applied. A p-value of ≤0.05 was taken as significant. R-Software was used for analysis of data. Results: Out of 352 cases, 302 (85.7%) were non-Neoplastic and 14% 48 (13.6%) were neoplastic. Two cases were of unremarkable pathology. Chronic cervicitis was observed as the most common lesion 293 (97%) out of 302 cases. Age of the patients ranged from 21-78 years. Most of the patients were in the reproductive age group: 21-49 years of age 274 (77.8%) cases. Mean mast cell count decreased from premalignant cases to malignant cases. In case of cervical intraepithelial lesion, mean mast cell count was found to be 26.5/10 High Per Field (HPF) and in cases of malignancy mean mast cell count of 17.5/10 HPF was observed. Mean mast cell count showed an inverse relationship with the grade of dysplasia and from dysplasia to cases of malignancy. Conclusion: Mast cell distribution and density support a diagnosis in addition to the routine histopathology, especially in cases of small cervical biopsies which are difficult to interpret.

Histochemical identification of mast cells in the pia mater of the rat

AIM: Identification of mast cells depends to great extent on the choice of the stain and the fixative, the type of mast cells and the tissue under study, and animal species. Based on this, this work aimed to find an optimal technique of histochemical revealing mast cells in the rat pia mater by testing three stains.&#x0D; MATERIALS AND METHODS: The study was performed on the brain of Wistar rats 5, 14, and 30 day-old (n=15). 67 m thick brain sections were Nissl stained with cresyl violet, toluidine blue, or methylene green and examined in Leica DM750 light microscope (Germany).&#x0D; RESULTS: Mast cells were found in pia mater of rats of all ages studied after staining with each of used stains. They could be determined by their metachromatic staining. Use of cresyl violet or toluidine blue resulted in intensive staining of all cellular elements of the nervous tissue, but mastocytes were metachromatically weakly stained on this background and in some cases could not be differentiated from the surrounding tissue. After usage of methylene green, the brain section staining was paler, but metachromasia of bright stained mast cells was more contrast and could distinctly be registered by digital photography.&#x0D; CONCLUSIONS: Metachromatic staining with methylene green is optimal for study of mast cells in the pia mater of the rat. It provides easy revealing of pial mastocytes and studying their morphologic features and is useful for morphometric analysis of mastocytes.

Reliability of cytological evaluation of mast cells from bronchoalveolar lavage fluid in horses: Intraobserver agreement and mast cell identification

SummaryEndoscopy, including bronchoalveolar lavage (BAL) fluid cytology, are invaluable tools for equine lower airway diagnostics. Objectives of the study were to evaluate the reliability of two staining methods, May–Grünwald–Giemsa (MGG) and toluidine blue (TB), for the evaluation of mast cells in cytospin smears from BAL fluid samples and the reliability of a 500‐cell differential cell count using both staining methods. Endoscopies and BAL fluid sampling were performed and BAL cytology was evaluated from cytospin smears. BAL cytology slides from 78 horses were evaluated. Three experienced observers evaluated the BAL cytology cytospin smears for the mast cell comparison study. The intra‐ and interobserver agreements were calculated using intraclass correlation coefficients (ICC). BAL cytology mast cell counts were significantly higher with the TB staining method compared with the MGG staining method. Observer agreements showed below acceptable agreement between observers for mast cell counts for both staining methods, even with fixed coordinates. Based on results from this study recommendation for BAL cytology staining would be to use both the MGG and the TB staining method, relying on the TB for the enumeration of mast cells.

Comparison of histochemical staining techniques for detecting mast cells in oral lesions

ABSTRACTMast cells are large cells with granular cytoplasm that participate in wound healing, angiogenesis and defense against pathogens. They also contribute to inflammation by initiating innate and acquired immunity. The granules of these cells exhibit characteristic staining properties. We investigated toluidine blue, astra blue, Alcian blue-pyronin Y and May-Grunwald Giemsa stains for mast cells in various oral lesions and assessed the efficacy of each for identifying mast cells. Sections were obtained from 10 each of diagnosed cases of inflammatory fibrous hyperplasia, periapical cyst, mild dysplasia, oral submucous fibrosis and oral squamous cell carcinoma and stained using the stains listed above. Mast cells were assessed for their presence, contrast of the mast cell in the connective tissue background and number. We found that May-Grunwald Giemsa stain was the best for identification of mast cells, although toluidine blue staining is less time-consuming. Overall we obtained better results using May-Grunwald Giemsa and toluidine blue for staining mast cells.

Utility of flow cytometry in canine primary cutaneous and matched nodal mast cell tumor

Mast cell tumors (MCT) are among the most frequent tumors in dogs, but studies regarding canine mast cell immunophenotype are lacking. The aim of this study was to assess the feasibility of flow cytometric analysis of MCTs, to describe canine MCTs immunophenotype(s), and to evaluate the ability of flow cytometry to detect mast cells in lymph node aspirates. Thirty-four primary canine MCTs and 12 draining lymph nodes were evaluated regarding the expression of CD117, IgE, CD11b, CD18, CD44, CD34, CD25 and CD45.Distinct populations attributable to mast cells and eosinophils were recognized based on light scatters and CD117 positivity. Common antigens (CD18, CD45, CD44) and CD117 were detected in all cases; positivity for IgE and CD11b was found in 28 (82%) and 23 (68%) cases respectively, while CD34 and CD25 were occasionally expressed. A single multicolor tube (IgE/CD117/CD11b/CD21/CD5) allowed the identification of mast cells in lymph nodes, showing a high correlation with cytology in quantifying mast cells infiltration. In conclusion, flow cytometric analysis can be applied to characterize canine MCTs and can be used to detect the presence of mast cells in lymph nodes. The immunophenotype abnormalities observed may be useful to confirm the neoplastic nature of such mast cells but the diagnostic usefulness of atypical antigen expression remains to be clarified.

Characterization of mast cell populations using different methods for their identification.

Mast cells are ubiquitous throughout the human tissues and play an essential role in physiology and pathology. For evaluation of patients with pathological conditions, mast cells were primarily detected using metachromatic staining with toluidine blue. In the last decades, the staining arsenal of pathologists was enriched with enzyme histochemical and immunohistochemical methods, and it was established that depending on species and tissue localization mast cells are not similar both in appearance and function. The aim of this study was to characterize different mast cell populations using the up-to-date methods of their identification. We compared standard metachromatic method for mast cells with enzyme histochemical detection of chloroacetyl esterase and with immunohistochemical detection of tryptase and chymase in human and rodent tissues. Combination of these methods allowed us to assay quantitatively mast cell populations in different organs of humans and rodents. Furthermore, we assessed the appropriate implementation of each of these methods for mast cell identification in diagnostic labs.

Histological and Histochemical Observations on Mast Cell and Glands in Chronic Tonsillitis.

Mast cell take active part in immune system of body, clinical manifestations are closely related to hypersensitivity. Reactions and potent biological mediators released by these cells are responsible for different clinical manifestation like allergic reaction. Frequent and important sites of these allergic reactions occur in-upper aero digestive tract, nasal, pharyngeal and respiratory allergies. The study aims to demonstrate different types of heparin in mast cells having role in tonsillitis. Present work is to study distribution and histochemical nature of mast cells in human palatine tonsil in patients suffering from chronic tonsillitis. 20 cases were studied during the study. Diagnosis was done on clinical criteria-Anterior pillar flushing. Expulsion of cheesy material from the tonsillar crypts on pressing with tongue depressor. Palpable jugulodigastric group of lymph nodes. Dissected Tonsillar material fixed into fixative-staining done. For qualitative histological observation Harris Haemotoxylene with eosin used as counter stain. Normal Histological study of mast cell like size, shape, granules were done. Distribution of mast cells in different parts of Tonsillar Tissue was observed. Histochemical study of mast cells to determine nature of reactive substance was done. Tonsil contains mucous glands, no granular tissue in present study of chronic inflammatory reactions feasible in form of fibrosis, lymphatic infiltration in epithelium. Morphology of mast cells with toluidine blue at pH 2 and 4.4 gave better picture. Mast cells had varied shape and size in different places and points of same field of focus, oval, elongated, fusiform, pleomorphic in shape. Nucleus is central ill-defined masked by granules. Cytoplasm contains mast cell granules that stained blue with Alcian blue stain, purple to bluish purple with toluidine blue. Distribution of mast cells in present study: Mast cells were found at all places mostly concentrated at capsules. Lamina propria-1-2/hpf, capsule-4-5/hpf, connective tissue septa-1-2/hpf. Histochemical Feature- In present study, histochemical study remained confined to connective tissue septa of mast cells and biochemical nature of Heparin contained in it. In present work, the identification of mast cells is based on metachromatic reactions of its granules with acidified toluidine blue at pH 2 and buffered toluidine blue at pH 4.4 to identify mast cell granules containing higher and lower sulphates of heparin.

Postmortem diagnosis of anaphylaxis in presence of decompositional changes

Eosinophil and activated mast cell identification in the spleen combined with mast cell tryptase determination in postmortem serum may diagnose fatal anaphylaxis with a high degree of certainty. Mast cell tryptase measurement and significance in corpses with decompositional changes remains however an issue of controversy. Analogously, immunohistochemistry in corpses with decompositional changes may be influenced by several mechanisms, including protein alteration, antigen diffusion and unspecific antibody binding to disrupted protein structures. The authors present an autopsy case involving a 55-year-old woman who unintentionally received clarithromycin. Due to difficult in administrative procedures, the postmortem examination was performed 96 h after death. Mast cell tryptase was measured in postmortem serum from femoral, aortic and right heart blood. The obtained results were consistent with mast cell activation. Histochemistry (Pagoda Red) and immunohistochemistry (anti-tryptase antibodies) allowed splenic eosinophils and mast cells to be detected. Based on the results of all postmortem investigations, the hypothesis of anaphylaxis following accidental clarithromycin administration was formulated.

Retinoic acid potentiates inflammatory cytokines in human mast cells: Identification of mast cells as prominent constituents of the skin retinoid network

Retinoic acid (RA), the active vitamin-A-metabolite, has well-established functions in skin homeostasis and in the immune system. Skin mast cells (MCs) combine traits of both structures, being of hematopoietic origin, but functional in the skin environment. It remains largely unknown whether mature MCs are targeted by the retinoid network. Here, we demonstrate that human skin MCs display substantial susceptibility to RA by which they are instructed to increase pro-inflammatory mediators (IL-1β, IL-8, TNF-α) but not histamine release. The effects are observed at physiological RA levels, in different microenvironments, and are largely donor-independent. RA susceptibility is owed to the cells' abundant expression of RARA, the receptor mediating MC cytokine responses. Unexpectedly, bioinformatics calculations on the FANTOM5 expression atlas revealed general enrichment of retinoid network components in MCs against other skin cells, and MCs rapidly upregulated RA responsive genes. In conclusion, MCs are important yet hitherto overlooked retinoid targets in the skin.

Evaluation of mast cells and eosinophils in odontogenic cysts: A histochemical approach

Background: Odontogenic cysts and tumors are most common benign destructive lesions in the oral cavity. These cystic lesions with its central fluid, reservoir of non-physiological composition, is in itself likely to provoke an inflammatory response in the surrounding host tissues, which may result in its formation and enlargement. Aims and Objectives: 1. To evaluate the number of mast cells and eosinophils in radicular cyst, keratocystic odontogenic tumor and dentigerous cyst and to intercompare it with the degree of inflammation. 2. To evaluate and intercompare the staining quality of toluidine blue and thionin for mast cells identification and Carbol Chromotrope and Congo red for eosinophils evaluation. Study Design: The study comprised of total 47 cases of which 20 were of radicular cyst, 15 were keratocystic odontogenic tumor and 12 were dentigerous cyst. Sections of 4μm thick were cut and stained with gold standard hematoxylin and eosin staining procedure for routine diagnosis. The amount of inflammation in each cyst was graded. They were further stained with toluidine blue and thionin for mast cells identification and Carbol Chromotrope and Congo red for eosinophils identification. The statistical analysis used was one way ANOVA (Analysis of Variance) and Pearson's Correlation Coefficient. Results: The mean number of cell count per high power field of mast cells was higher than the eosinophils. On correlating with degree of inflammation the results came out to be statistically significant. The staining quality for mast cells was equally good with toluidine blue and thionin, whereas Carbol Chromotrope had a significantly better staining quality than Congo red in case of eosinophils. Conclusion: The higher number of mast cells detected in odontogenic cysts could contribute in the release of inflammatory mediators involved in the pathogenesis of odontogenic cysts formation and enlargement. The histochemistry using various stains has proved to be promising in identification of mast cells and eosinophils.

Mast cell research.

The role of mast cells in allergy remained unrevealed until the observation that they contained histamine in 1953, and then the discovery of immunoglobulin E (IgE) in 1966, nearly a century after Ehrlich's first publication. After the discovery of IgE, myeloma-derived IgE from Peter Shackford, who made a great contribution to mankind by providing 40 liters of plasma in the year prior to his death, was distributed to many researchers. This accelerated the exploration of the mechanisms involved in allergic reactions, especially regarding the role of mast cells in IgE-mediated reactions. The identification of mast cells as a progeny of a bone marrow hematopoietic stem cell in 1977 led us to the successful in vitro culture of mast cells. Along with the development of molecular biological techniques, the structure of the high-affinity IgE receptor (FcεRI) was determined in 1989. Thus, we now understand the whole molecules the expression of which is changed when mast cells are activated via FcεRI cross-linking. However, the physiological and pathological roles of mast cells, especially where IgE is not involved, are not yet fully understood. It will be necessary to determine the mechanisms involved in the 'non-IgE-mediated' steps of mast cell activation in allergic or other diseases.