Mast Cell Density Research Articles

Duodenal cholinergic tuft cell number is increased in functional dyspepsia

Low-grade duodenal inflammation has recently been identified in patients with functional dyspepsia (FD). Chemosensory tuft cells were reported to be associated with gastrointestinal diseases. We therefore assessed duodenal tuft cell density and microinflammation in patients with FD to determine whether these measures could serve as useful biomarkers, and also correlated tuft cell density and microinflammation in FD patients. Duodenal biopsy specimens were obtained from patients with FD and from controls. Tuft cells, eosinophils, and mast cells were immunochemically stained with specific antibodies. Tuft cells were identified by immunostaining for doublecortin-like kinase 1 (DCLK1); cholinergic tuft cells were assessed by double staining for choline acetyltransferase (ChAT) and DCLK1. Immune-type tuft cells were assessed by IL-25 mRNA expression using real-time PCR. The density of intramucosal eosinophils and mast cells was significantly higher in the duodenum of FD patients than in controls. The density of tuft cells was significantly higher in the duodenum of FD patients compared with controls, and significantly correlated with eosinophil density in the duodenum of FD patients and controls. Moreover, a fraction of ChAT-positive cells was DCLK1 positive; all duodenal DCLK1+ tuft cells were ChAT-immunoreactive in FD and in control subjects. Cholinergic tuft cell density was higher in the duodenum of patients with FD and significantly correlated with eosinophil density. Further studies are needed to investigate the pathophysiological significance of tuft cells in FD and may provide valuable clues to the pathophysiology of FD.

Levels of circulating mast cell progenitors and tumour‑infiltrating mast cells in patients with colorectal cancer.

The role of mast cells in colorectal cancer (CRC) has been an area of intense interest. Mast cell density is closely related to CRC development and prognosis. The identification of mast cell progenitors (MCps) in peripheral blood provides an opportunity to explore the frequency and distribution of mast cells in the circulation and tumour microenvironment of patients with CRC at different disease stages. The aim of the presents study was to investigate the changes of MCps and mast cells in CRC. Flow cytometry was used to measure the circulating frequency of MCps in 37 patients with CRC and 12 healthy control (HC) patients, and the frequency of mast cells in tissue from 15 patients with CRC and 7 patients with haemorrhoids. In the present study, lower levels of circulating MCps in patients with CRC were found, which was significantly related to CRC development. After surgery, the frequency of circulating MCps was significantly increased. However, the frequency of mast cells in tumour tissues was lower than that in adjacent normal tissues and compared with HC tissues and was not associated with CRC progression.

Effects of Disodium Cromoglycate Treatment in the Early Stage of Diabetic Nephropathy: Focus on Collagen Deposition.

Inflammation is part of the pathophysiology of diabetic nephropathy (DN), and mast cells (MCs) appear to increase in number within the kidney of humans and animals with diabetes. Disodium cromoglycate (CG) not only inhibits the degranulation of MCs but also has several secondary effects that may improve inflammation. However, little is known about the effects of CG treatment on kidney collagen deposition and myofibroblast population in animals with type I diabetes (DM1). Data presented here suggest that the increases in the density and activity of MCs within the kidney in the early stages of DN contribute to tubulointerstitial collagen deposition, even in the absence of alterations in the renal myofibroblast population. Moreover, CG treatment showed renoprotective effects in rats with DM1, which appear to be linked to its mast cell stabilizing property and its ability to avoid some detrimental morphofunctional alterations.

Selected Articles from This Issue

Approximately 20% of breast cancers harbor human epidermal growth factor receptor 2 (HER2/ERBB2) overexpression or amplification. KN026, a novel HER2 bispecific antibody, has been shown to overcome resistance to HER2 target therapies in preclinical models. Zhang and colleagues conducted a phase I trial of KN026 in patients with HER2-positive metastatic breast cancer who had progressed on prior anti-HER2 therapies. KN026 was well tolerated, and treatment led to an objective response rate of 28.1%. Furthermore, the authors associated CDK12 co-amplification with an improved response to KN026, supporting further assessment of this potential biomarker. Although these results are interesting, further clinical trials of this novel bispecific antibody are warranted.Metastasis is a common occurrence in patients with osteosarcoma. Although current therapeutics have shown limited ability to reduce metastasis, CCR2+ monocytes have emerged as an actionable target for the prevention of lung metastasis. Regan and colleagues conducted a clinical trial in pet dogs with spontaneous advanced metastatic osteosarcoma to assess high-dose losartan, an angiotensin receptor inhibitor, in this context. In combination with the kinase inhibitor toceranib, losartan inhibited the CCL2-CCR2 pathway, was well tolerated and led to a clinical benefit rate of 50%. These results support further clinical study of losartan, especially human clinical trials.Although immunotherapy has provided a benefit to many patients, predictive biomarkers are still needed to more effectively guide treatment in patients with advanced renal cell carcinoma (RCC). To identify potential biomarkers in patients with advanced RCC treated with avelumab plus axitinib or sunitinib, Bilen and colleagues conducted a post hoc analysis of data from the phase 3 JAVELIN Renal 101 trial. The authors found that a low neutrophil-to-lymphocyte ratio (NLR) was associated with longer progression-free survival, overall survival, and objective response rate. These results support the continued development of NLR as a predictive biomarker for immunotherapy in patients with advanced RCC.Prior studies have shown that cabozantinib, an inhibitor of VEGFRs and additional tyrosine kinases, is effective for the treatment of metastatic clear cell renal cell carcinoma (mccRCC). However, it is unclear whether the mechanism of this agent is via its targeting of VEGFR or another target. To address this question, Denize and colleagues assessed angiogenesis markers in patients treated with cabozantinib or everolimus as part of the METEOR trial. Microvascular density and mast cell density, both markers of angiogenesis, were both associated with longer progression-free survival. Furthermore, patients treated with cabozantinib had improved progression-free survival, overall survival, and objective response rate compared with those treated with everolimus; importantly, these results were not dependent on levels of microvascular density or mast cell density. These results support the activity of cabozantinib in patients with mccRCC and suggest that VEGFR-independent effects may be part of the mechanism of this agent.

Mast cell density and its clinical relevance in Waldenström's macroglobulinemia.

The presence of numerous mast cells (MCs) mixed with tumor cells in the bone marrow (BM) is a hallmark of the diagnosis of Waldenström's macroglobulinemia (WM). MCs have been shown to support lymphoplasmacytic cell growth, but there is thus far no demonstration of the prognostic impact of BM MC density in WM. We investigated BM MC density by sensitive and specific digital quantification, allowing the analysis of a large area infiltrated by BM tumor cells. A total of 65 WM patients were investigated, including 54 at diagnosis and 11 at relapse. Tryptase and CD20 immunohistochemisty staining was performed on contiguous sections of deparaffinized BM trephine biopsies. After numerization of each section, the BM surface area was manually marked out, excluding the bone framework and adipocytes to limit the analyses to only hematopoietic tissue. MCs were assessed using a digital tool previously used to quantify immune‐cell infiltrates on tumor‐tissue sections. Deep next‐generation sequencing and allele‐specific PCR were used to explore the MYD88 and CXCR4 mutational status. MC density was heterogeneous among the WM patients. An optimal MC density threshold (> 56 MC.mm–2) was defined according to ROC curve analysis of overall survival. A higher MC density (> 56 MC.mm–2) was associated with greater BM involvement by WM lymphoplasmacytic cells and less hepatosplenic involvement (p = 0.023). Furthermore, MC density significantly correlated with a higher ISSWM score (p = 0.0003) in symptomatic patients. Patients with a higher MC density showed shorter median OS (56.5 months vs. nonreached, p = 0.0004), even in multivariate analysis after controlling for other predictive variables, such as age, ISSWM score, and CXCR4 mutational status. In conclusion, MC density can be accurately measured in WM patients using a specific digital tool on well‐outlined hematopoietic tissue surfaces. High MC density is associated with aggressive features and a poor clinical outcome, emphasizing the need for further investigation of the involvement of MCs in the pathophysiology of WM.

Canine Mammary Neoplasms - Evaluation of Tumor Microenvironment

Background: The tumor microenvironment is an important target of studies in different types of neoplasms. Understanding the role of general components such as immune, vascular and fibroblastic cells has the objective of contributing to prognosis and treatment. The aim of this study was to evaluate the relationship between mast cells and angiogenesis in benign and malignant mammary neoplasms by investigating the role of degranulation and microlocation of mast cells and neoformed vessels in canine mammary neoplasms.Materials, Methods & Results: Mammary glands (n = 122) from 50 female dogs submitted to mastectomy without chemotherapy were evaluated and categorized into 3 groups: control group (n = 46); malignant group (n = 57) and benign group (n = 19). Lymph nodes without changes (n = 59) and with metastases (n = 6) were also evaluated. To evaluate the MCD (mast cell density) and angiogenesis, Toluidine Blue (0.1%) and Gomori’s Trichrome techniques were performed and adapted from previous studies. Photomicrographs of 10 hotspot areas on a 40x objective lens of the mammary glands and lymph nodes were captured to assess MCD and angiogenesis. In the absence of these areas, random fields were captured. For the mammary glands of the malignant and benign groups, 20 fields were analyzed, as the analysis considered the microlocation (peritumoral and intratumoral). Counting was performed manually using ImageJ software version 1.42q by 2 observers. The statistical analysis were performed using SPSS software version 19.0. The most frequent histological type in the malignant group was carcinoma in mixed tumor (68.42%; 39/57) and in the benign group was benign mixed tumor (57.89%; 11/19). Female dogs without breed pattern were more frequently affected represented 70% of the animals and the mean age was 9 years and 8 months ± 3 years and 1 month. The granulated density of mast cells and peritumor vessels was higher in the malignant group (P = 0.03; P = 0.02). There was also a positive correlation between intratumor and total vessel density and mast cell density. There was no significance between the malignant and benign groups in regard with fibrosis density.Discussion: In this study were observed a greater density of blood vessels in malignant group, suggesting the participation of blood vessels for neoplastic proliferation. Furthermore, these vessels were located in the peritumoral region as in previous studies. The positive correlation between MCD and blood vessels was similar to a previous study performed in canine breast carcinomas and breast cancer in women. Regarding microlocation, another study also found higher MCD in the peritumoral region than in the intratumoral region of canine carcinomas. Although there are already studies for this purpose in cases of oral squamous cell carcinoma in humans, we believe this is the first study to investigate the role of mast cell degranulation in mammary neoplasm of bitches. The MCD was not significant among the malignant and benign groups and in the mammary glands of the control group the MCD was higher, as observed by other studies. Future studies should be associated the survival time and the presence of metastases in order to confirm the findings. In view of these findings, we may conclude that a higher density of mast cells is related to a higher density of blood vessels and that these are more abundant in malignant neoplasms, which reinforces the crucial role of angiogenesis in the neoplastic development.Keywords: tumor microenvironment, mammary tumor, mast cells, angiogenesis, bitches.

A Murine Kitl Allele Regulates Skin Mast Cell Density across 58 Collaborative Mouse Cross Strains

Mast cells contain chemicals needed for the body’s response to extrinsic challenges in various tissues, including the skin. Little is known about the genetic control of mast cell numbers in unchallenged skin. Overabundance of mast cells in mastocytosis, resulting from their excess production in the bone marrow, is characterized by somatic KIT alteration, although such variants are not always found in cutaneous mastocytosis. It appears that many germline variants can predispose to this condition, including those near OTX2, ABCA2, CYP2B5, RPTN (Nedoszytko et al., 2020), CEBPA, LICO1412, and TBLXR1 (Galatà et al., 2021).

Presence of Increased Mast Cells in Infants and Children with Volume and Variety Limited Intake.

Background: Reports indicate patients with feeding difficulties demonstrate signs of inflammation on biopsies, notably eosinophilia, but it is unknown whether mast cell density contributes to variety or volume limitation symptoms. The aim of our study was to evaluate eosinophil and mast cell density of EGD biopsies in pediatric patients with symptoms of decreased volume or variety of ingested foods. Methods: We conducted a single-center, retrospective chart review of EMRs for all new feeding clinic patients between 0 and 17 years of age. Patients were categorized by symptoms at the initial visit as well as eosinophil and mast cell densities in those with EGD biopsies. Ten patients were identified as controls. Results: We identified 30 patients each with volume and variety limitation. Antral mast cell density was increased in 32.1% of variety-limited patients, 37.5% of volume limited patients, and in no controls; Duodenal mast cell density was increased in 32.1% of variety-limited patients, 40.6% of volume-limited patients, and in no controls. Conclusions: In both variety- and volume-limited patients, antral and duodenal mast cell densities were increased. These associations warrant further investigation of the mechanism between mast cells and development of feeding difficulties, allowing more targeted pediatric therapies.

Mechanistic insight into the synergism of IL-27 and IL-28B in regulation of benzo(a)pyrene-induced lung carcinogenesis associated ROS/NF-κB/NLRP3 crosstalk

AimOur previous work depicted that benzo(a)pyrene (BaP)-induced lung cancer associated pulmonary redox imbalance and inflammation were effectively regulated by the combinatorial treatment of IL-27 and IL-28B. So in continuation of that finding the present study was designed to reveal the inflammation regulating signaling network modulated by IL-27 and IL-28B treatment related to BaP-induced lung cancer. MethodsMale Swiss albino mice were treated with BaP to induce lung tumor. Then they received individual as well as combinatorial treatment of IL-27 and IL-28B. At the end of the experimental schedule, the expression of NF-κB signaling proteins, the formation of NLRP3 inflammasome complex and IL-18; IL-17A expression in the lung were observed using Western blot and RT-PCR. The tissue and serum levels of some proinflammatory cytokines were also studied using ELISA. Mast cell density was also studied using toluidine blue staining procedure. ResultsTreatment with IL-27 or IL-28B alone was successful to regulate the expression of NF-κB signaling proteins and NLRP3 complex in some cases but best attenuation was observed in animals who received both IL-27 and IL-28B in combination. In combination, it was successful in down-regulating the expression of p-ERK1/2 and in reducing the accumulation of mast cells in the lung tissue associated with BaP-induced lung carcinogenesis. The impaired PPARγ expression was also reinstated upon combination treatment. ConclusionAltogether, the treatment in combination with IL-27 and IL-28B is an effective regimen to attenuate the ROS/NF-κB/NLRP3 axis associated with BaP-induced lung carcinogenesis.

Peritumoural Mast Cell Density in Invasive Breast Carcinoma: Possible Antitumourigenic Effect with Potential Role for Immunotherapy

Introduction: The interaction of cancer cells and the host within the tumour microenvironment plays a major role in determining the outcome of cancers. Mast cells are part of the innate immune system that interact with tumour cells and known to have pro-tumourigenic and antitumourigenic action through their mediators. Their role in the outcome of invasive breast cancer is still not clear with studies showing both a beneficial role as well as a role in tumour progression. Aim: To assess Mast Cell Density (MCD) in tissues of invasive carcinoma of breast and compare with clinicopathological parameters to infer their biological significance. Materials and Methods: The study was a retrospective cross-sectional study carried out at the Department of Pathology, SRM Medical College Hospital & Research Centre, SRMIST, Kattankulathur, Chennai, India on 51 cases of invasive carcinoma of breast received between January 2011 and July 2013 and the study conducted between August to November 2013. Clinical parameters and histopathological findings were recorded. Mast cells were clearly demonstrated in tissue using Toluidine Blue stain at pH 2.3. The MCD within primary malignant breast tumour tissue (mastectomy specimens, n=51) was assessed using an eyepiece grid and expressed as no. of cells/per sq. mm. Statistical analysis of all parameters was performed using SPSS software (v 17.0) to analyse association of MCD with clinicopathological parameters. Results: The MCD was significantly higher in malignant breast tissue compared to non neoplastic breast tissue (p<0.0001). No significant difference in MCD was observed between tumour size groups (T1, T2, and T3) (p=0.6967). No statistically significant difference in MCD was observed between the four histological types observed (p=0.892). The majority of the tumours were of Grade 2 category (n=37), followed by Grade 3 (n=11) and Grade 1 (n=3). No significant difference in MCD was observed between the three histological grades (p=0.785). The MCD was significantly higher in patients without lymph node metastasis compared to the group with lymph node metastasis (p=0.0023*). The MCD in invasive carcinoma of breast, post-chemotherapy group was significantly higher than that in invasive carcinoma of breast pre-chemotherapy group (p=0.0064). Conclusion: The current study shows significantly increased MCD at the periphery of the carcinoma breast tissue in patients without lymph node metastasis compared to those with lymph node metastasis. Hence, a potential antitumourigenic and beneficial role of mast cells in invasive primary breast carcinoma could be inferred and may serve as one of the prognostic indicators for patient stratification for various treatment options including immunotherapy

Status of Mast Cells in Autopsy Specimens of Prostate: A Cross-sectional Study

Introduction: Mast cells are found in areas rich in connective tissues and beneath epithelial surfaces. Mast cells have been extensively studied for their orchestration of allergic reactions and autoimmunity. Mast cells infiltrate various prostatic lesions in varying concentrations. Autopsy specimens had not been investigated extensively in the previous literature. Aim: To find out a quantitative estimation of mast cells and the association of the number of mast cells in various prostatic lesions that included both inflammatory and neoplastic lesions in autopsy cases. Materials and Methods: A cross-sectional, analytical study was carried out in the Department of Pathology, R.G. Kar Medical College and Hospital, Kolkata, India from April 2017 to March 2018. Sixty autopsy specimens of the prostate were dissected from the deceased males above 30 years of age. Four to six paraffin embedded sections from different lobes and peri-urethral areas were taken. Haematoxylin and Eosin (H&E) stained sections for histopathological diagnosis and toluidine-blue stain after water mounting to demonstrate mast cells by its metachromasia were performed. Mast cell densities were estimated by a light microscope under high power magnification (400X) on an average of 100 fields. Gross and microscopic findings were recorded. Data analysis correlation was done using Statistical Package for the Social Sciences (SPSS) software version 18.0. Mean and standard deviations were determined for different prostatic lesions. Group means were compared using the student’s t-test. For statistical significance p-value of less than 0.05 was considered. Results: A total of 60 autopsy specimens of the prostate were studied comprising 8 (13.5%) specimens of normal prostate, which acted as a control, 6 (10%) specimens of prostatitis, 27 (45%) specimens of Benign Hypertrophy of Prostate (BHP), 12 (20%) specimens of BHP with Prostatic Intraepithelial Neoplasia (PIN), 3 (5%) specimens of prostatitis with focal PIN and 4 (6.5%) specimens of prostatic adenocarcinoma. Mast Cell Density (MCD) was higher in prostatitis {6-8 per High Power Fields (HPF)}, compared to normal (1-3/HPF) and BHP (3-5/ HPF), lowest in adenocarcinoma (1-2/HPF) and intermediate in PIN (2-4/HPF). Conclusion: Mast cell density was the lowest in prostatic adenocarcinoma and significantly higher in prostatitis, probably due to a lack of antitumour immunity in higher grades, whereas it was significantly higher in chronic non specific prostatitis possibly because of inflammatory response.

Low Tumor Infiltrating Mast Cell Density Reveals Prognostic Benefit in Cervical Carcinoma.

Objectives: Research on the role of mast cells (MCs) in cervical tumor immunity is more limited. Therefore, our study aimed to evaluate the prognostic value of MCs and their correlation with the immune microenvironment of cervical carcinoma (CC). Methods: The Cancer Genome Atlas (TCGA) data was utilized to obtain the degree of immune infiltration of MCs in CC. Meanwhile, this study retrospectively collected patient clinical characteristic data and tissue specimens to further verify the relevant conclusions. Mast cell density (MCD) was measured by the CIBERSORT algorithm in TCGA data and immunohistochemical staining of tryptase in CC tissues. Finally, differentially expressed genes (DEGs) of TCGA data were performed using “limma” packages and key gene modules were identified using the MCODE application in Cytoscape. Results: The results showed MCs were diffusely distributed in CC tissues. Moreover, we found that low tumor-infiltrating MCD was beneficial for overall survival (OS) in the TCGA cohort. Consistent conclusions were also obtained in a clinical cohort. In addition, a total of 305 DEGs were analyzed between the high tumor-infiltrating MCD and low tumor-infiltrating MCD group. Seven key modules, a total of 34 genes, were screened through the MCODE plug-in, which was mainly related to inflammatory response and immune response and closely correlated with cytokines including CSF2, CCL20, IL1A, IL1B, and CXCL8. Conclusion: In short, high tumor-infiltration MCs in CC tissue was associated with worse OS in patients. Furthermore, MCs were closely related to cytokines in the tumor microenvironment, suggesting that they collectively played a role in the immune response of the tumor. Therefore, MCD may be a potential prognostic indicator and immunotherapy target of CC.

Prognostic significance of mast cells and vascular density in prostatic adenocarcinoma.

Though mast cells infiltrate solid tumors, the exact role of mast cells in tumor biology is controversial. Mast cell density (MCD) may vary depending on its location in the tumor and tumor vascularity. MCD may influence the tumor aggressiveness. This study evaluates MCD and tumor vascularity in different histopathological grades of adenocarcinoma prostate. Descriptive study with purposive sampling. The subjects of study were 42 adenocarcinoma patients. 20 cases were of intermediate grade (Gleason score 2-7) and 22 were of high-grade (Gleason score 8-10). Histological diagnosis was made by examining sections stained with hematoxylin and eosin. Additional sections from the same block were stained for mast cells using Giemsa stains as per standard protocol. Mast cell count was done in minimum six random high-power microscopy fields in four different regions- intratumoral, peritumoral, stromal and perivascular regions. SSPS software version 13.0. Descriptive statistics, Student's t test and ANOVA test. In high-grade adenocarcinoma, mast cell counts were higher in perilesional, stromal and perivascular regions, whereas it was lower in intralesional areas as compared to the intermediate grade. However, statistical significance was observed only for the perivascular region. There was significantly higher number of blood vessels in high-grade adenocarcinoma as compared to intermediate grade adenocarcinoma. In this study, perilesional mast cells and vascularity increased with increased severity of adenocarcinoma. These findings suggest a possible influence of mast cells on the tumor microenvironment such as vessel density and aggressiveness of tumor. However, further studies are required to substantiate results of this study.

High Mast Cell Density Predicts a Favorable Prognosis in Patients with Pancreatic Neuroendocrine Neoplasms

Introduction: Mast cells are involved in allergic diseases, immune regulation, and tumor microenvironment modulation, with both pro- and anti-tumorigenic functions, and could serve as a prognostic factor in various cancers. However, their potential role in pancreatic neuroendocrine neoplasms (PanNENs) is largely unknown. Here, our aim was to investigate the presence of mast cells in PanNENs and evaluate their association with clinicopathological parameters and other common tumor-infiltrating immune cells. Methods: Tissue microarrays containing PanNEN samples from 187 patients were constructed and stained immunohistochemically for CD117, CD15, CD68, CD3, CD4, and CD8. Immune cells were counted from four high-power fields (HPFs; ×400) at maximal concentrations, and the mean counts were calculated per HPF. The cutoff values were set by X-tile. Results: The median (interquartile range) counts of CD117⁺ mast cells, CD15⁺ neutrophils, CD68⁺ macrophages, CD3⁺ T cells, and CD4⁺ T cells were 3.5 (2.0–6.0), 3.0 (1.3–6), 3.8 (2.5–5.8), 13 (8.0–24.0), and 2.0 (1.0–4.0)/HPF, respectively. CD8⁺ T cells were not detected. The cutoff values for these immune cells were 1.5/HPF, 6/HPF, 4.8/HPF, 32.5/HPF, and 2/HPF, respectively. Low mast cell density was correlated with higher grades, noninsulinoma, and advanced stages. Moreover, high mast cell infiltration was associated with elevated CD4⁺ T cell and CD15⁺ neutrophil counts. Multivariate analysis revealed that high mast cell density was an independent predictor of prolonged progression-free survival in the entire cohort; in pancreatic neuroendocrine tumors; and in intermediate-grade, noninsulinoma, and advanced stage subgroups. Conclusions: These findings suggest a protective role of mast cells in PanNENs.

Histomorphometry of mast cells in the convexity of human intracranial dura mater.

Mast cells, known as pro-inflammatory effector cells, are immunocytes present in the meninges and may be involved in the pathophysiology of migraine. This study aims to evaluate the histomorphometric parameters of mast cells located in the convexity of the human intracranial dura mater. For this, samples of intracranial dura mater from eight human fresh cadavers were collected between 8- and 24-h post-mortem. The whole samples were fixed and, subsequently, two fragments of 1.5cm² each were cut from four different areas of the dura mater convexity, containing a segment of the middle meningeal artery, totaling 64 fragments. After histological processing, the fragments were submitted to microtomy (5 and 10µm), stained with toluidine blue (0.1%), or immunohistochemically labeled for tryptase, and analyzed using optical microscopy. The following histomorphometric parameters were evaluated: distance from mast cells to vessels, the density of mast cells, and percentage of mast cells with degranulation. Histomorphometric analyzes showed a higher density of mast cells in the vicinity of blood vessels (arterial and venous), with distances around 0-150µm. A greater number of mast cells was detected near venous vessels in the periosteal layer (17.0±10.1cells/mm²) than in the meningeal layer (14.1±7.0cells/mm²) (p<0.05). Mast cells from the region close to the superior sagittal sinus were found in greater quantity close to the venous vessels (16.7±10.1cells/mm²) than to the arterial vessels (11.2±7.5cells/mm²) (p<0.05). In short, in the convexity of the human intracranial dura mater, mast cells are located close to blood vessels, with a greater number of cells next to the venous vessels of the periosteal layer and in the proximal region of the superior sagittal sinus.

Covid-19 caseload in the UK—assessments and mitigations

The variability of mast cell density within and between leprosy skin lesions was examined as a basis for future studies, and whether the number of mast cells in the lesion...

A Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells.

Chronic pancreatitis (CP) is characterized by pancreatic inflammation, fibrosis, and abdominal pain that is challenging to treat. Mesenchymal stromal cells (MSCs) overexpressing human alpha-1 antitrypsin (hAAT-MSCs) showed improved mobility and protective functions over native MSCs in nonobese diabetic mice. We investigated whether hAAT-MSCs could mitigate CP and its associated pain using trinitrobenzene sulfonic acid (TNBS)-induced CP mouse models. CP mice were given native human MSCs or hAAT-MSCs (0.5 × 106 cells/mouse, i.v., n = 6–8/group). The index of visceral pain was measured by graduated von Frey filaments. Pancreatic morphology and pancreatic mast cell count were analyzed by morphological stains. Nociceptor transient receptor potential vanilloid 1 (TRPV1) expression in dorsal root ganglia (DRG) was determined by immunohistochemistry. hAAT-MSC-treated CP mice best preserved pancreatic morphology and histology. MSC or hAAT-MSC infusion reduced abdominal pain sensitivities. hAAT-MSC therapy also suppressed TRPV1 expression in DRG and reduced pancreatic mast cell density induced by TNBS. Overall, hAAT-MSCs reduced pain and mitigated pancreatic inflammation in CP equal to MSCs with a trend toward a higher pancreatic weight and better pain relief in the hAAT-MSC group compared to the MSC group. Both MSCs and hAAT-MSCs might be used as a novel therapeutic tool for CP-related pain.

Decline in Mast Cell Density During Diffuse Alveolar Damage in Idiopathic Pulmonary Fibrosis

Mast cells (MCs) are known to be involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF), although their role in acute exacerbations of IPF has not been investigated. The aims of the study were to evaluate the numbers of MCs in fibrotic and non-fibrotic areas of lung tissue specimens of idiopathic pulmonary fibrosis (IPF) patients with or without an acute exacerbation of IPF, and to correlate the MC density with clinical parameters. MCs of IPF patients were quantified from surgical lung biopsy (SLB) specimens (n = 47) and lung tissue specimens taken at autopsy (n = 7). MC density was higher in the fibrotic areas of lung tissue compared with spared alveolar areas or in controls. Female gender, low diffusion capacity for carbon monoxide, diffuse alveolar damage, and smoking were associated with a low MC density. MC densities of fibrotic areas had declined significantly in five subjects in whom both SLB in the stable phase and autopsy after an acute exacerbation of IPF had been performed. There were no correlations of MC densities with survival time or future acute exacerbations. The MC density in fibrotic areas was associated with several clinical parameters. An acute exacerbation of IPF was associated with a significant decline in MC counts. Further investigations will be needed to clarify the role of these cells in IPF and in the pathogenesis of acute exacerbation as this may help to identify some potential targets for medical treatment for this serious disease.

Mast Cells Modulate the Immune Response and Redox Status of the Gastrointestinal Tract in Induced Venom Pathogenesis

The pathogenesis of Androctonus autralis hector (Aah) scorpion venom involved cellular and molecular mechanisms resulting in multi-organ dysfunction. However, little is reported about the effects of venom on the gastrointestinal axis. Mast cells (MCs) are known to play a crucial role in modulating immune response of the gut. This study aims to investigate the involvement of this cell type in venom-induced gastric and intestinal disorders in a time course (3 and 24h). The obtained results revealed that Aah scorpion venom induced inflammatory cell infiltration as shown by the increase of the myeloperoxidase and eosinophil peroxidase activities. Overexpression of the c-kit receptor (CD117) severely imbalanced the redox status with depletion of antioxidant systemic accompanied by gastrointestinal tissue damage. Moreover, an increased level of lactate dehydrogenase in the serum was correlated with tissue injuries. Pharmacological inhibition of MCs targeting tyrosine kinase (TK) reduces the generation of reactive oxygen species and normalizes catalase, and gluthation S-transferase activities to their physiological levels. In addition, histopathological alterations were restored after pretreatment with c-kit receptor inhibitor associated with a considerable reduction of MC density. Interestingly, obtained results indicate that MCs might be involved in gastric modulation and intestinal inflammation through c-kit signaling following sub-cutaneous Aah venom injection.

Mast cells in luminal vs non-luminal breast cancers

Background: Tumor growth and development is determined by the mutual interaction between the cancer cells themselves and the microenvironment. It contains various elements, including immune cells. Of all, mast cells have one of the most controversial roles. The aim of the present study was to evaluate the expression of mast cell tryptase in the luminal and non-luminal subtypes of breast cancer and establish a possible link between infiltration with MCs and expression of hormone receptors. Material and methods: The experimental study included 80 cases of breast carcinomas that were analyzed immunohistochemically in order to establish the molecular profile and the expression of tryptase, a specific marker of mast cells. The data were processed using the SPSS program. Pearson’s coefficient (r) and the other values were considered statistically significant in case of p≤0.05. Results: Both intratumoral mast cells (MCit) and peritumoral mast cells (MCpt) correlated with the expression of hormone receptors for estrogen (ER) and progesterone (PR). Thus, the following relations were established: MCit and ER (r=0.343, p=0.002), MCpt and ER (r=0.394, p=0.000295) and MCpt and PR (r=0.386, p=0.000409). Statistically significant correlations between HER2 expression and mast cells content have not been established. Conclusions: Mast cells invasion, peri- and intratumoral, is strongly influenced by the expression of hormone receptors. The luminal subtypes of breast cancer are characterized by a higher density of mast cells.