Mast Cell Density Research Articles

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.

MP39-15 YAP EXPRESSION PLAYS IMPORTANT ROLES IN MALIGNANT AGGRESSIVENESS BY REGULATING THE INFILTRATION OF CD57 + NATURAL KILLER CELLS, CD68 + MACROPHAGES, AND MAST CELLS AND THE EXPRESSION OF VEGF-A AND PD-L1 IN CLEAR CELL RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (MP39)1 Sep 2021MP39-15 YAP EXPRESSION PLAYS IMPORTANT ROLES IN MALIGNANT AGGRESSIVENESS BY REGULATING THE INFILTRATION OF CD57+ NATURAL KILLER CELLS, CD68+ MACROPHAGES, AND MAST CELLS AND THE EXPRESSION OF VEGF-A AND PD-L1 IN CLEAR CELL RENAL CELL CARCINOMA Kojiro Ohba, Yasuyoshi Miyata, Junki Harada, Tsuyoshi Matsuda, Tsubasa Kondo, Asato Otsubo, Yuta Mukae, Hidenori Ito, Hiroki Kurata, Kensuke Mitsunari, Hideki Sakai, Tomohiro Matsuo, and Yasushi Mochizuki Kojiro OhbaKojiro Ohba More articles by this author , Yasuyoshi MiyataYasuyoshi Miyata More articles by this author , Junki HaradaJunki Harada More articles by this author , Tsuyoshi MatsudaTsuyoshi Matsuda More articles by this author , Tsubasa KondoTsubasa Kondo More articles by this author , Asato OtsuboAsato Otsubo More articles by this author , Yuta MukaeYuta Mukae More articles by this author , Hidenori ItoHidenori Ito More articles by this author , Hiroki KurataHiroki Kurata More articles by this author , Kensuke MitsunariKensuke Mitsunari More articles by this author , Hideki SakaiHideki Sakai More articles by this author , Tomohiro MatsuoTomohiro Matsuo More articles by this author , and Yasushi MochizukiYasushi Mochizuki More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002054.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The Hippo signalling pathway is known as a critical regulator of malignant aggressiveness, and Yes-associated protein (YAP) is the most important downstream effector in this pathway. Although, YAP has pro-oncogenic activities, its detailed mechanisms are not fully understood. Recently, YAP has been reported to play important roles in tumour immunity, by regulating tumour-infiltrating lymphocytes and vascular endothelial growth factor (VEGF)-A and programmed cell death ligand 1 (PD-L1). However, the relationships between YAP expression, the densities of macrophages, natural killer (NK) cells, and mast cells; and VEGF-A and PD-L1 expression in human clear cell renal cell carcinoma (ccRCC) are not clear. METHODS: In 157 ccRCC tissues, the expression levels of YAP and VEGF-A were evaluated by immunohistochemistry, according to the percentage of positively stained cells and staining intensity. The densities of CD57+ NK cells, CD68+ macrophages, and mast cells were calculated as the number of positively stained cells per high-power field (HPF). All examinations were performed using immunohistochemical staining. RESULTS: Positive expression of YAP was significantly associated with high tumor grade, high pT stage, the presence of metastasis, and poor cause-specific survival in patients with ccRCC (p<0.001). CD57+ NK cell density was significantly lower (p<0.001) in YAP-positive tissues (mean±SD, 22.1 ± 8.0/HPF) than in YAP-negative tissues (33.1 ± 8.4/HPF). In contrast, CD68+ macrophage density was significantly higher (p<0.001) in YAP-positive tissues (44.2±14.5/HPF) than that in YAP-negative tissues (29.3±9.8/HPF). Similarly, YAP expression was positively correlated with mast cell density (p<0.001). However, H-scores of PD-L1 were significantly lower (p<0.001) in YAP-positive tissues (6.6±9.6) than in YAP-negative tissues (3.1±6.0). In addition, a similar positive correlation was detected between YAP expression and VEGF-A expression (p<0.001). CD57+ NK cell, CD68+ macrophage, and mast cell density and VEGF-A and PD-L1 expression were all significantly associated with pathological features. CONCLUSIONS: YAP expression was positively associated with tumour growth, invasion, and metastasis by stimulating the infiltration of CD58+ macrophages and mast cells into cancer tissues; increasing the expression of VEGF-A and PD-L1 in cancer cells; and suppressing the infiltration of CD57+ NK cells. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e710-e710 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kojiro Ohba More articles by this author Yasuyoshi Miyata More articles by this author Junki Harada More articles by this author Tsuyoshi Matsuda More articles by this author Tsubasa Kondo More articles by this author Asato Otsubo More articles by this author Yuta Mukae More articles by this author Hidenori Ito More articles by this author Hiroki Kurata More articles by this author Kensuke Mitsunari More articles by this author Hideki Sakai More articles by this author Tomohiro Matsuo More articles by this author Yasushi Mochizuki More articles by this author Expand All Advertisement Loading ...

In vivo photoprotective potential evaluation and in vitro genoprotective of red propolis from Apis mellifera in Rio Grande do Norte (semiarid region), Brazil

The objective of this study was to evaluate the levels of phenols, total flavonoids, as well as the antioxidant, genoprotective, and photoprotective activities of the red propolis ethanolic extract produced by Apis mellifera. Different concentrations of the extract were analyzed In vitro by spectrophotometry. The photoprotective effect of the extract was evaluated In vivo in 30 Wistar rats divided into three groups: Group 1 - the skin received no topical application of the extract and was not subjected to ultraviolet irradiation; Group 2 - the skin was not subjected to topical application of the extract and was irradiated; Group 3 – the skin underwent topical application of the extract and was irradiated. The skin was evaluated macroscopically, and the density of inflammatory cells, mast cells, necrotic cells, and collagen fibers were quantified. The extract contained high levels of phenols and flavonoids, with antioxidant and genoprotective capacity, protecting the skin from irradiation. In group II, erythemas, blisters, and superficial crusting were observed. No significant differences in mean values of mast cell density and collagen fibers were observed between groups I and III. It was concluded that the ethanolic extract of red propolis exerted genoprotective and photoprotective effects by promoting satisfactory absorbance of ultraviolet radiation and was able to protect the skin from lesions induced by UVB irradiation.

Mast cell infiltration and activation in the gallbladder wall: Implications for the pathogenesis of functional gallbladder disorder in adult patients

BackgroundFunctional gallbladder disorder (FGD) is characterized by recurrent biliary colic with a decreased gallbladder ejection fraction on cholescintigraphy but absence of visible gallbladder abnormalities on ultrasonography. FGD is generally regarded as a primary gallbladder motility disturbance, however, the underlying pathophysiology remains largely unknown. In this study, we investigated the potential role of mast cells in the pathogenesis of FGD by examining mast cell density and activation in the gallbladder wall. DesignTwenty adult patients with FGD undergoing cholecystectomy were included in the study. Seven patients with no gallbladder disease were served as controls who were subject to incidental cholecystectomy during abdominal surgery such as partial hepatectomy. The density of mast cells in the gallbladder wall was assessed by immunohistochemistry and by toluidine blue special stain. Mast cell activation was evaluated by calculating the percentage of degranulated mast cells on toluidine blue stain. ResultsCompared to the controls, patients with FGD showed a significant increase in mast cell infiltration in the gallbladder walls. Peak mast cell accumulation was predominantly located in the inner muscular layer of the gallbladder wall. Mast cell activation was also markedly increased in the FGD group as evidenced by significantly enhanced mast cell degranulation. ConclusionsMast cell infiltration and activation were significantly increased in the muscular wall of gallbladders from FGD patients, suggesting potential involvement of mast cells in the compromised gallbladder motility in adult patients with FGD.

Abstract 1494: IgE receptor-activated human mast cells have potent anti-cancer properties

Abstract The purpose of this study was to test the hypothesis that human mast cells (MC) have anti-tumor mediators that can be targeted to tumor specific antigens, induced to release these mediators, and cause cancer cell apoptosis. Breast cancer (BC) continues to be a significant cause of mortality for women in the United States. The oncogene HER2/neu is overexpressed in BC and is validated target for cancer therapeutics. New immunotherapy strategies and combinations of immune agents with non-redundant mechanisms of action are needed. The role of human tissue mast cells (MC) in the pathology of many cancers is not known. Nonetheless, high densities of MC are associated with favorable prognosis in certain types of cancer such as BC suggesting an anti-tumor effect. We previously reported that human adipose cells can be differentiated into autologous, fully functional MC (ADMC) capable of releasing mediators upon FcϵRI stimulation that induce BC cell death of cell suspensions of SK-BR3. Further data is presented demonstrating the anti-tumor effects of ADMC using BC tumor masses. The ADMC, sensitized with breast cancer-specific IgE anti-HER2/neu, bound to and were activated by, HER2/neu-positive human BC cells. The anti-HER2/neu IgE-sensitized ADMC bound to, infiltrated, and induced apoptosis of HER2/neu-positive BT-474 BC tumor masses as determined by time-lapse, live cell confocal imaging. Specific, HER2/neu IgE-mediated binding was also verified in vivo using immunocompromised xenograft models. Further studies are warranted to determine if tumor-targeted, autologous MC may be a new way to treat solid tumors. Citation Format: Chris Kepley, Mohammad Ferrydouni, Mona Motaghed, Kristen Dellinger. IgE receptor-activated human mast cells have potent anti-cancer properties [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1494.

Mast Cell Density and Its Clinical Relevance in Waldenstrom's Macroglobulinemia

Background. Waldenström's macroglobulinemia (WM) is characterized by a lymphoplasmacytic infiltration of the bone marrow (BM) along with a serum monoclonal IgM and includes MYD88 L265P and CXCR4 mutations in around 90% and 25% respectively (Treon, NEJM 2012; Hunter, Blood 2014). CXCR4WHIMmutations confer worse outcome and are associated with larger BM involvement and less adenopathies (Treon, Blood 2014). One hallmark and histological criteria for WM diagnosis is the presence of numerous mast cells (MC) segregating with tumor cells in the BM (Waldenström, Acta Haematologica 1958). MC have been shown to support lymphoplasmacytic cell growth, through CD154/CD40 signaling (Tournilhac, Ann Oncol 2006), but there is so far no clear demonstration of the prognostic impact of BM MC density in WM.Aim. We proposed to investigate BM MC density by using sensitive and specific digital quantification, allowing the analysis of large tumor cell infiltrated BM area, in order to assess its clinical relevance in WM.Methods. A total of 65 WM patients were investigated, including 54 pts at diagnosis and 11 at relapse. Mutational status could be determined in 35 pts: allele specific PCR found MYD88 L265P mutation in 32/35 pts (91%) and deep next-generation analysis found CXCR4WHIMmutation in 7/35 (20%) pts. Diagnostic and treatment criteria for WM fulfilled recommendations of the 8th international WM workshop (Castillo, BJH 2016 ; Leblond, Blood 2016). MC density was explored using a digital tool previously used for quantifying immune cells infiltrates on tumor tissues sections (Galon, Science 2006). Tryptase and CD20 immunohistochemisty stainings were done on contiguous sections of deparaffinized BM trephine biopsies. After numerization of each section, BM surface area was manually marked out, excluding bone framework and adipocytes, in order to limit subsequent analyses to hematopoietic tissue. We then defined optimal thresholds for horseradish peroxidase signal detection. MC were counted up with “Immunoscore module” (Definiens Developer XT), on the hematopoietic tissue of the whole BM section : MC density was automately recorded as the number of tryptase positive cells per unit of selected bone marrow tissue surface area.Results. MC density was found to be heterogeneous over BM, with a mean of 106 MC.mm-2 of hematopoietic tissue (Figure 1). Higher MC density (> 100 MC.mm-2) was associated with larger BM involvement by WM cells (BM deep infiltration (p=0.039) and diffuse tumor pattern (p=0.003)) and with less frequent spleen involvement (p=0.011) and a trend towards less lymph node (p=0.072) and liver (p=0.054) involvement. Higher MC density was also associated with features of advanced disease such as anemia (<115g.L-1 ; p = 0.041), thrombocytopenia (<100G.L-1 ; p=0.01) and lower albumin rate (<35g.L-1 ; p=0.03)). Furthermore MC density was 194 MC.mm-2 in patients with high IPSS, 82.4 MC.mm-2 in those with intermediate IPSS and 67.9 MC.mm-2 in those with low IPSS (p=0.0003). Regarding outcome, patients with higher MC density had a shorter median OS (56.5 months vs non reached in patients with low MC density, p = 0.0139)) (Figure 2). Among the pts scheduled to receive a 1st line treatment for an active disase (n=43) and molecularly characterized (n=20), those with CXCR4WHIM mutations had a significantly higher MC density (240.7 MC.mm-2vs 90.9 MC.mm-2 for CXCR4 WT pts ; p=0.0221).Conclusion. By using specific digital tool on well-outlined hematopoietic tissue surface, MC density can be accurately measured in WM patients. High MC density is associated with aggressive features, poor clinical outcome and possibly with CXCR4WHIM mutation. [Display omitted] DisclosuresYsebaert:Janssen: Consultancy, Research Funding, Speakers Bureau. Leblond:Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria; Novartis: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hermine:Hybrigenics: Research Funding; INatherys: Equity Ownership, Research Funding; AB Science: Equity Ownership, Honoraria, Patents & Royalties, Research Funding; Novartis: Research Funding; Celgene: Research Funding. Guieze:GILEAD: Other: Educational Presentation; ABBVIE: Other: Educational Presentation; JANSSEN: Other: Educational Presentation. Tournilhac:Janssen: Honoraria, Other: travel funding; AMGEN: Other: Travel funding, Research Funding; ROCHE: Honoraria, Other: Travel funding, Research Funding; GILEAD: Honoraria, Other: Travel Funding, Research Funding; Abbvie: Honoraria, Other: Travel funding.

Comparative Analysis of Mast Cell Density in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma

Introduction: Oral squamous cell carcinoma (OSCC) is one of the most common malignancies of the oral cavity. One of the foremost cells recruited near the tumor front is the mast cells. Mast cells produce angiogenic mediators such as fibroblast growth factor (FGF), transforming growth factor (TGF), tumor necrosis factor, (TNF), and the vascular endothelial growth factor (VEGF) 1. which are increased in precancerous lesions and found in more abundance in OSCC.Accumulation of mast cells around the tumor margins and their release of potent pro-angiogenic and angiogenic factors may represent a tumor-host interaction which probably favors tumor progression. The progression of oral lesions from dysplasia to oral squamous cell carcinoma is characterized by an “angiogenic switch” that is associated with an increase in the neovascularization of the subepithelial lamina propria, which may be considered an indicator of malignant transformation. 2MCs also represent a rich source of proteases, especially ofmast cell tryptase and chymase, which directly degrade the extracellularmatrix through their proteolytic activity and thus indirectly stimulate angiogenesis and facilitate invasion and metastasis. Theliterature has proven that mast cells can be an indicator of increased angiogenesis and hence can help in the prediction of carcinogenesis, its progression, and also the prognosis of the malignant lesions.Aim of the Study: To compare the number, morphology, and distribution of mast cells in different grades of oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) and to study their role in tumor growth and pathogenesisMaterials and Methods: A total of 39 cases, which included 13 cases of dysplasia and 26 of OSCC were included in the study. Tissue sections were stained with H&amp;E and 1% toluidine blue was used to evaluate mast cells. Mast cells were counted manually using an ocular grid throughout the tissue sections in 10 representative grid fields in a stepladder fashion. (40x magnification).The mean mast cell density (MCD) of 10 fields was calculated and was expressed as mean (standard deviation) per mm3,4. Mast cells were then categorized as typical, atypical, or granular mast cells and statistically analyzed.5Result: In the present study, there is a decrease in the number of mast cells with severe grades of dysplasia and poorer grades of oral squamous cell carcinoma.&#x0D; ConclusionMast cells may induce the tumor progression by providing a mitogenic stimulation or angiogenesis-the hallmark of the tumor growth and metastasis through the release of various mediators.

Succinate‐Induced Tuft Cell Hyperplasia Enhances FFA2/5‐HT Mediated Anion Secretion in Mouse Duodenum

Tuft cells are one of luminal chemosensing components in the small intestine, while the role of tuft cell in mucosal secretory responses to luminal chemicals such as short-chain fatty acids (SCFA) has not been elucidated. We thus hypothesized that tuft cell hyperplasia may increase the secretory responses to luminal SCFA due to the increased cholinergic signals since tuft cells express choline acetyltransferase (ChAT). Tuft cell hyperplasia was induced by oral sodium succinate (NaSuc, 100 mM) in the drinking water for 7 days. Sodium propionate (NaP, 10 mM, m), the selective free fatty acid receptor 2 (FFA2) agonist 4-CMTB (10 µM, s), or the TRPA1 agonist allyl isothiocyanate (AITC, 1 mM, m) were applied to the mucosal (m) or serosal (s) baths of an Ussing chamber mounted with muscle-stripped mucosa-submucosa preparations of mouse proximal duodenum or jejunum. The density of tuft cells (doublecortin-like kinase 1; DCLK1), enteroendocrine L cells (proglucagon, glucagon-like peptide-2), and enterochromaffin (EC) cells (5-HT, tryptophan hydroxylase 1; TPH1) were assessed by real-time PCR and immunostaining. NaSuc treatment significantly increased the number of DCLK1-positive tuft cells in the duodenal and jejunal villi. mRNA expression of DCLK1 and FFA2 were increased in the duodenal and jejunal mucosa, whereas TPH1 was increased only in the duodenal mucosa, and ChAT was increased in the jejunal mucosa, but proglucagon was unchanged in both. 5-HT-positive mast cell density rather than EC cell density was increased in the duodenum. Isc in response to luminal NaP was enhanced in the jejunum, which was atropine sensitive. In contrast, Isc responses to serosal 4-CMTB and luminal AITC were enhanced in the duodenum, which were mediated by 5-HT3 and 5-HT4 receptors. These results suggest that NaSuc differentially enhances secretory responses, with 5-HT signals in the duodenum and with cholinergic signals in the jejunum. These data may be implicated in the pathogenesis of functional dyspepsia (FD), since increased duodenal mast cell density and enhanced 5-HT signals are present in FD patients.

Correlation of Mast Cell and Angiogenesis in Oral Lichen Planus, Dysplasia (Leukoplakia), and Oral Squamous Cell Carcinoma.

ObjectiveThe aim of this study was to compare and correlate mast cell density (MCD) and microvessel density (MVD) between normal oral mucosa, oral lichen planus, various grades of dysplasia, and oral squamous cell carcinoma (OSCC).Materials and MethodsThe study comprised a total of 75 samples, of which 65 were archival tissue blocks of histopathologically confirmed cases, which included 10 cases of oral lichen planus, 25 cases of dysplasia (mild [n=10], moderate [n=10], and severe [n=5]), and 30 cases of OSCC (well differentiated [n=10], moderately differentiated [n=10], and poorly differentiated [n=10]), and 10 samples of normal oral mucosa. All the sections were immunohistochemically stained with anti-CD34 and counterstained with toluidine blue stain. Mean MCD and MVD were determined and analyzed using ANOVA test and compared between the lesions using Tukey HSD test. Pearson’s correlation coefficient test was used to correlate these two factors between various lesions.ResultsMean MCD and mean MVD were found to be increased in all the lesions compared to normal oral mucosa, and the values were statically significant. Overall, MCD and MVD showed a significant positive correlation (r=0.640).ConclusionIncrease of MCD and MVD and their positive correlation in all the lesions have emphasized their role in the pathogenesis and disease progression.

Mucosal eosinophils, mast cells, and intraepithelial lymphocytes in youth with rumination syndrome.

Rumination syndrome has been associated with increased duodenal eosinophils and intraepithelial lymphocytes in adults. The aims of the current study were to assess densities of antroduodenal eosinophils and mast cells and duodenal intraepithelial lymphocytes in youth with rumination syndrome and to compare cell densities in those with and without abdominal pain or early satiety. Twenty-eight youth fulfilling Rome IV criteria for rumination syndrome who had undergone endoscopy were identified and compared to 10 controls. Antral and duodenal biopsies were assessed to determine densities of eosinophils, mast cells, and intraepithelial lymphocytes. Cell densities were also compared between rumination patients with and without abdominal pain and those with and without early satiety. Antral mast cell (peak 18.5±6.5 vs. 12.5±2.7) and eosinophil (peak 9.6±5.2 vs. 4.9±2.1) densities were significantly greater in patients with rumination syndrome as compared to controls. Duodenal intraepithelial lymphocyte densities were also increased in rumination syndrome (18.9 ± 5.1 vs. 11.7 ± 1.5; p<.001). Associations were independent of the presence of abdominal pain or early satiety. In conclusion, we found an increase in eosinophil and mast cell densities in the gastric antrum and an increase in intraepithelial lymphocytes in the duodenum in youth with rumination syndrome which was independent of the presence of abdominal pain or early satiety. These findings suggest a potential role for inflammation in the pathophysiology of rumination syndrome. Future studies should address whether treatment directed at these cells are beneficial in treating rumination syndrome.

Synovial Immunohistological Biomarkers of the Classification of Undifferentiated Arthritis Evolving to Rheumatoid or Psoriatic Arthritis.

Background: Undifferentiated arthritis (UA) is defined as an inflammatory arthritis that does not fulfill criteria for a definite diagnosis. Delay in reaching a specific diagnostic and therapy may lead to impaired functional outcomes. Our aim was to identify synovial biomarkers associated with definitive diagnostic classification in patients with UA.Methods: DMARD-naïve UA patients with available initial synovial tissue (ST) and a final diagnosis of rheumatoid arthritis (RA) or psoriatic arthritis (PsA) during follow-up were included and compared with patients with well-defined disease (RA or PsA). Clinical, arthroscopic, and pathological data were compared between groups. Pathology included quantitative immunohistochemical (IHC) analysis of cell types and human interferon-regulated MxA. Principal component analysis (PCA) was performed to extract disease patterns.Results: One hundred and five patients were included: 31 patients with DMARD-naïve UA (19 evolving to RA and 12 to PsA during a median follow up of 7 years), 39 with established RA, and 35 with established PsA. ST from the UA group showed higher macrophage density compared with the established RA and PsA groups. Patients with UA evolving to RA (UA-RA) showed higher MxA expression and CD3+ T-cell density compared with established RA. UA patients evolving to PsA (UA-PsA) showed increased vascularity and lining synovial fibroblast density compared with established PsA. Synovitis of UA-PsA patients showed more mast cells and lining fibroblasts compared with UA-RA. No between-group differences in local or systemic inflammation markers were found.Conclusions: Our results show differences in the cellular composition of UA synovium compared with RA and PsA, with higher density of the cellular infiltrate in the UA groups. Initial expression of the interferon inducible gene MxA could be a biomarker of progression to RA, while higher mast cell and fibroblastic density may be associated with PsA progression.

Survey of Mast Cell Density in Transitional Cell Carcinoma

Background & Objective:Transitional cell carcinoma (TCC) is the world's seventh most common tumor and forms more than 90% of urinary bladder tumors. Invasive tumors are associated with poor prognosis, even with surgical treatment and chemotherapy. Some studies have found that an increase in the number of mast cells in TCC is related to the tumor grade and its aggressiveness. This study investigated the relationship between mast cell density (MCD) and features of TCC (tumor stage, grade, prognosis, and recurrence). Methods:Fifty-one cases with TCC were selected, and MCD was determined by immunohistochemistry (IHC) and Giemsa staining. Mortality rate and tumor recurrence were recorded. Results:The MCD mean was higher in high-grade tumors than in low-grade tumors (in IHC method: 9.127 vs 5.296; in Giemsa method: 5.512 vs 2.608). Also, the MCD mean in dead patients was higher than in survived patients (in IHC method: 11.390 vs 6.211; in Giemsa method: 7.460 vs 3.35). Patients with tumor recurrence showed a higher MCD mean than those without recurrence (in IHC method: 9.395 vs 5.475; in Giemsa method: 5.715 vs 2.931). Conclusion:Using mast cell tryptase and Giemsa, MCD may be associated with a positive correlation with tumor grade in TCC. Correlations between MCD, recurrence, prognosis, and tumor stage are probably caused by the effect of tumor grade (all with P<0.05).

Mast Cells and Proteins Related to Myofibroblast Differentiation (PAR-2, IL-6, and TGFβ1) in Salivary Cancers: A Preliminary Study.

Salivary gland neoplasms represent an important group of cancers in the head and neck and myoepithelial cells play a key role on the development these tumors. This study evaluated the distribution of mast cells and related proteins (PAR-2, TGFβ1, IL-6) to the myofibroblastic differentiation in malignant tumors of salivary glands with and without myoepithelial differentiation. Immunohistochemical assessement for tryptase mast cells, SMA, PAR-2, TGFβ1, IL-6 was performed in 10 cases of polymorphous low-grade adenocarcinoma, 14 cases of mucoepidermoid carcinoma (MEC) and 10 cases of adenoid cystic carcinoma. When the density of mast cells were compared between tumors, their density was significantly higher in MEC (P=0.08). Tumors with high expression of PAR-2 (79.4%) exhibited a high density of mast cells. Myofibroblasts were more frequent in malignant tumors with low expression (<50%) of cell masts. Individual analysis of the tumors showed no significant difference between the expression of PAR-2, IL-6, TGFβ1, and myofibroblasts. When the density of mast cells, myofibroblasts and the expression of PAR-2 protein, IL-6, and TGFβ1 were compared, it was no statistically significant difference between tumors with and without myoepithelial differentiation. The results of present study suggest a possible participation of mast cells and especially of PAR-2 in the development and progression of malignant salivary cancers, regardless of myoepithelial content.

The role of intestinal mast cell infiltration in irritable bowel syndrome.

As an essential part of the immune system, mast cells (MCs) play an important role in the pathogenesis of irritable bowel syndrome (IBS). Accumulating evidence has identified altered MC count and density in intestinal mucosa of patients with IBS; however, conflicting findings yield inconsistent conclusions. Currently, most studies have suggested intestinal MC infiltration in IBS patients. Considering the pivotal role of MCs in IBS, it is necessary to achieve a better understanding about the pathological changes in the intestine. The risk factors for IBS, including dietary habits, psychological factors, infection, and dysbiosis, are implicated to induce intestinal MC infiltration. Mechanistically, food may trigger immune-related allergic reactions and affect the intestinal microbiota activity. Some exogenous pathogens and altered profile of commensal bacteria promote intestinal MC recruitment through promoted release of chemokines from epithelial cells or direct activation of the immune system. In addition, psychological factors may affect the microenvironment where MCs live. MCs have been proven to interact with the enteric neurons and other immunocytes, evidenced by the close proximity of MCs to neurons and regional altered immune system components. A variety of mediators released by the enteric neurons, immunocytes, and MCs per se, such as neurotrophins, neuropeptides, cytokines, and chemokines, may have stimulant effects on MCs by modulating the survival, proliferation, and recruitment process of MCs in the intestine. In this review, the associations between IBS and intestinal MC density and the underlying mechanisms are discussed.

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.

Involvement of tryptase-positive mast cells and angiogenesis in the growth of inflammatory odontogenic cysts.

Inflammatory periapical lesions are characterized by infiltration of different immune cell types, the functions of which depend on an effective vascular network. This study aimed to evaluate the mast cells density (MCD) in inflamatory odontogenic cysts capsules concerning microvascular density (MVD), microvascular area (MVA), and microvascular perimeter (MVP), and correlate such findings with the type of lesion, intensity of the inflammatory infiltrate, and thickness of the epithelial lining. Twenty inflamatory dentigerous cysts (IDCs), twenty radicular cysts (RCs), and twenty residual radicular cysts (RRCs) were submitted to immunohistochemical analysis using anti-tryptase and anti-CD34 antibodies. RCs exhibited the highest MCD, MVD, MVA, and MVP indexes (p = < 0.001, p = 0.008, p = 0.003 and p = < 0.001, respectively), and lesions with inflammatory infiltrate grade III showed the highest MVD (p = 0.044). Considering epithelial thickness, a higher MVP index was identified in lesions with hyperplastic epithelium (p = 0.018). In IDCs, RCs, and RRCs, a strong positive correlation was observed between MVA and MVP (r = 0.950 and p = < 0.001; r = 0.914 and p = < 0.001; r = 0.713 and p = < 0.001, respectively). In IDCs, a moderate correlation was observed between MCD and both MVA and MVP (r = 0.660 and p = 0.002; r = 0.634 and p = 0.003, respectively). These results suggest that tryptase-positive mast cells might play an important role in the angiogenic activity of IDCs, while RCs had the highest indexes. Our findings also confirmed that the intensity of the inflammatory infiltrate and epithelial thickness influence angiogenesis.

Study of the Nerve Apparatus and Mast Cells in the Hearts of Old Rats

A comparative study of the nerve structures and the density of mast cells in the heart of rats aged 3–4 and 23 months was carried out with histological and histochemical methods and the immunohistochemical markers PGP 9.5, tyrosine hydroxylase (TH), and synaptophysin. It was found that tissues innervation decreases with aging in all studied heart areas, particularly, sympathetic innervation. A decrease in sympathetic plexus density and the presence of dystrophic and degenerative changes in TH-immunopositive axon terminals were registered. It was also demonstrated that the mast cell population in old animals increases in the connective tissue of the pericardial, in the epicardium, and the myocardium of atria and ventricles region upon a decrease in sympathetic innervation. It is suggested that the increase in the number of mast cells in the heart during aging occurs in response to a deficiency in catecholamines and is related to the mast-cell secretion of biologically active substances (heparin, histamine, and serotonin), which help maintain local tissue homeostasis and adaptive and compensatory reactions of the animal heart.

Immunohistochemical analysis of the arterial supply and mast cells of the trigeminal ganglion

The aim of this study was to quantify the distribution of microvessels and mast cells in all three parts of the trigeminal ganglion (TG). Statistical analyses were applied to investigate possible micromorphological regional differences in their density. Five serially sectioned human TGs were prepared for CD34 and mast cell tryptase immunostaining. The following quantifications were performed in microscopic fields of three parts of the TG: microvessel density (MVD), mast cell density (MCD) and ganglionic cell count. The density of CD34-positive microvessels was not significantly different in any of the three observed parts of the TG. The distribution of neurons showed no significant statistical difference in three parts of the TG. There was no difference in the density of tryptase-positive mast cells within the TG, but there was an abundant presence of mast cells in the periganglionic dural and subdural tissues, a finding hitherto not reported. We can say that there is a homogenous vascular pattern within the TG which excludes local predominance in pathogenesis of trigeminal neuralgia. Second, and more important, the finding of peri-trigeminal mast cells indicates their important role in migraine pain and confirms their degranulation as the main therapeutic goal for this condition.

Epithelial and Connective Tissue Changes in Oral Submucous Fibrosis ?? A Morphometric Analysis

Introduction: Oral Submucous Fibrosis (OSF) is a common oral health problem in the Indian subcontinent. It was first reported by Schwartz and defined by Pindborg. OSF is within a group of conditions that are classified under potentially malignant disorders of the oral cavity. Current evidence suggests that are coline in the areca nut is the key factor in initiating the disease process. Objective: The purpose of this study is to conduct the morphometric analysis of the epithelial and selected connective tissue changes related to capillaries and to determine mast cell density in different grades of OSF. Method: The study comprises 25 cases of OSF in varying grades (according to Pindborg and Sirsat classification) retrieved from the archives of department of oral pathology. The slides were prepared and stained in Hematoxylin and Eosin stain and 1% toluidine blue. All the slides are being studied under Trinocular research microscope Olympus BX-53 and further quantified in image capture software for morphometric analysis. Result: Morphometrical analysis of epithelial thickness and connective tissue changes highlightening the parameters of capillary density, luminal diameter and circumferences of the capillaries have shown that varying degree of alterations in different grades of OSF when the severity of the disease increases. This study also included the mast cell density analysis which have proven to undergo changes as the severity of the disease progress.

Decreased Presence of Mast Cells in the Bursa Premacularis of Proliferative Diabetic Retinopathy

Introduction: We previously reported that the intravitreal activities of chymase and tryptase were more increased in the patients with macular hole (MH) and epiretinal membrane (ERM) than in those with proliferative diabetic retinopathy (PDR) and that the source of these serine proteases might be mast cells in the bursa premacularis (BPM). The purpose of this study was to compare the density of mast cells in BPM samples obtained from MH, ERM, and PDR patients. Methods: BPM and vitreous core samples were first collected during vitrectomy from eyes afflicted with vitreoretinal diseases (MH: 6 eyes, ERM: 3 eyes, and PDR: 9 eyes), and then were stained with hematoxylin, toluidine blue, antibodies against chymase and tryptase, and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay kit. Results: Hematoxylin nuclear staining showed fewer positive-staining cells in the BPM samples obtained from PDR patients than in those obtained from MH and ERM patients. Toluidine blue staining of the BPM revealed metachromasia in the mast cells of the patients with MH and ERM, but not those of the patients with PDR. In addition, immunostaining using anti-chymase and anti-tryptase antibodies showed that the BPM samples were more intensely stained than the vitreous core samples from the patients with MH and ERM and that both tissue samples were poorly stained in the patients with PDR. The apoptotic cells were more frequently observed in the BPM samples from patients with MH than in those from patients with PDR. Conclusions: These findings indicated that lower activities of chymase and tryptase in the vitreous of PDR patients appeared to be attributable to the decreased presence of mast cells in the BPM. The lack of mast cells in the BPM might be related to the pathogenesis of PDR.