Possible Role Of Mast Cells Research Articles

Ultrastructural features of tumor-associated mast cells in parasympathetic paragangliomas (chemodectomas) of the neck.

The mechanisms of the pathogenesis of neck paraganglioma (PGL) and the possible role of mast cells (MCs) in its development and metastasis are still poorly understood. We analyzed MCs' morphologic characterization, activation, and the properties of their cytoplasmic/released granules in PGLs, using light and transmission electron microscopy. Paragangliomas showed a large tumor-associated MC population both in the connective tissue layers of the tumor and between the tumor cells. Notably, MCs were presented by a high expression of specific proteases, size variation, polymorphism, and variable ultrastructural phenotype of granules. A massive number of granules were released surrounding the degranulated MCs while the integrity of MC membrane was maintained. Granules were electron-dense with or without a membrane, ranging from 0.2 to 0.8 μm in diameter. MC plasmalemma was not found at the site of MC-collagen fibrils contact, whereas the secretome and fibrils were directly contacted. We observed direct and mediator-based interactions between MCs and paraganglioma cells. The latter preserved their membrane integrity when MC granules were not in proximity. The effects of the MC secretome on the paraganglioma microenvironment demonstrated its pathogenetic role in tumor progression and allow its application to new diagnostic criteria and the development of protocols for personalized therapy. RESEARCH HIGHLIGHTS: Ultrastructural analysis reveals novel regulatory effects of mast cells via diverse secretory pathways on the pathogenesis of parasympathetic paraganglioma, including fibrous extracellular matrix remodeling and mediator-based interactions between MCs and cells of the tumor microenvironment.

The role of mast cells in the pathogenesis of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is one of major causes of chronic noncommunicable diseases and mortality worldwide. The roles of macrophages, T-lymphocytes, neutrophils, and other cells in the development of chronic inflammation in this disease are well studied, but more and more researchers have focused on mast cells (MC) in recent years.The aim of this work is to summarize the data of experimental and clinical studies on the possible role of MCs in the pathogenesis of COPD. To this end, the review analyzed data on the relationship between MCs and respiratory function parameters in COPD, as well as the distribution of MCs subpopulations in different parts of the respiratory tract. The involvement of proteases (chymase and tryptase) in the development of inflammatory and fibrotic changes in COPD is discussed. The review presents research findings that indicate the possible involvement of chymase in pulmonary artery remodeling, increased secretion of mucins, and slowing down the airway epithelial repair. The role of MC tryptase in the development of fibrotic changes in the lungs and airways in COPD is also highlighted. A separate section of the review is devoted to chemokines that promote MC migration and their specific receptor. Chemokines play a special role in the development of inflammation in COPD.Conclusion. The available data suggest that MCs play a major role in the pathogenesis of COPD. Because of the inconsistency of some results, further clinical studies in larger cohorts of patients are needed.

The Role of Mast Cells in the Pathogenesis of Covid-19

Background: The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019 in Wuhan. The problem of COVID-19 treatment is still relevant, and it is necessary to study in details the pathogenesis of COVID-19, including the role of mast cells (MCs). Aim: The aim of the review is to reveal the role of MCs, their receptors and mediators in the pathogenesis of the COVID-19. Results: This review demonstrates a possible role of MCs in the pathogenesis of COVID-19. Conclusion: MCs may be key elements of inflammation caused by COVID-19. MCs express various receptors on their surface that ensure the interaction of SARS-CoV-2 and MCs. Activated MCs release inflammatory cytokines, chemokines and proteases, which are involved in both the protective function and hyperinflammation in COVID-19. Keywords: Сoronavirus Disease 2019, mast cells, mast cells' mediators, mast cells' receptors

Mast Cell-Tumor Interactions: Molecular Mechanisms of Recruitment, Intratumoral Communication and Potential Therapeutic Targets for Tumor Growth.

Mast cells (MCs) are tissue-resident immune cells that are important players in diseases associated with chronic inflammation such as cancer. Since MCs can infiltrate solid tumors and promote or limit tumor growth, a possible polarization of MCs to pro-tumoral or anti-tumoral phenotypes has been proposed and remains as a challenging research field. Here, we review the recent evidence regarding the complex relationship between MCs and tumor cells. In particular, we consider: (1) the multifaceted role of MCs on tumor growth suggested by histological analysis of tumor biopsies and studies performed in MC-deficient animal models; (2) the signaling pathways triggered by tumor-derived chemotactic mediators and bioactive lipids that promote MC migration and modulate their function inside tumors; (3) the possible phenotypic changes on MCs triggered by prevalent conditions in the tumor microenvironment (TME) such as hypoxia; (4) the signaling pathways that specifically lead to the production of angiogenic factors, mainly VEGF; and (5) the possible role of MCs on tumor fibrosis and metastasis. Finally, we discuss the novel literature on the molecular mechanisms potentially related to phenotypic changes that MCs undergo into the TME and some therapeutic strategies targeting MC activation to limit tumor growth.

Role of mast cells in surgically resected specimens of appendices

Introduction: Mast cells are very closely linked to diseases and have a significant role in inflammatory process. The functions of mast cells depends on release of preformed granules. The aims and objectives of present study are to investigate the possible role of mast cells in pathogenesis of appendicitis. Materials and Methods: This prospective study was conducted on 100 surgically resected appendicectomy specimens at our hospital. Study period was from March 2016 to February 2017 for a period of one year. Histopathological diagnosis was made and status of mast cells was studied. Results: In this study presence of mast cells and its relationship with appendicitis was studied and it was found that increased number of mast cells were noted in inflammatory conditions of appendix. Presence of mast cells has an impact on pathology of appendix. Keywords: Appendix, Mast cells, Toluidine blue, Appendicitis.

Expression and mechanism of mast cell activating molecules and their antibodies in allergic rhinitis and nasal polyps

Objective:To analyze the relationship and mechanism of mast cell with allergic rhinitis and nasal polyps. Method:From January 2018 to June 2018, all the inpatients in Otolaryngology Department were examined by nasal endoscopy and CT before operation. They were divided into three groups: 30 patients with allergic rhinitis（AR group） and 30 patients with nasal polyps（NP group） as the experimental group; 30 patients with nasal septum correction after partial inferior turbinectomy alone as the control group（N group）. Clinical data, peripheral blood and nasal mucosa were collected. The percentage of eosinophils in peripheral blood was detected by automatic hematology analyzer. The levels of anti-IgE antibody, FcεRIα and anti-FcεRIα antibody in serum were detected by ELISA. The levels of serum IgE were detected by velocity scattering turbidimetry. HE was used to observe the histopathological changes in the three groups. Immunohistochemical method was used to analyze the expression of tryptase and FcεRIα in the experimental group and the control group. Result:The percentage of eosinophils, IgE, anti-IgE antibody, FcεRIα and anti-FcεRIα antibodies in AR group were significantly higher than those in control group（P<0.05）; the percentage of eosinophils, FcεRIα and anti-FcεRIα antibodies in NP group were significantly higher than those in healthy control group（P<0.05）. There was no significant difference in IgE and anti-IgE antibodies among three groups（P>0.05）. The eosinophil percentage, IgE and anti-IgE antibody levels in AR group were significantly higher than that in NP group（P<0.05）; there were no differences in FcεRIα and anti-FcεRIα antibody levels between AR group and NP group（P>0.05）; There was no significant difference in eosinophil infiltration between the two groups; The brown tryptase-positive mast cells and FcεRIα-positive mast cells were found in the submucosa and interstitium of nasal mucosa. Conclusion:The high expression of FcεRIα and its antibody in the serum of patients with allergic rhinitis and nasal polyps indicated that this antibody system was involved in the occurrence and development of allergic rhinitis and nasal polyps. Local allergy with mast cells as the core might play an important role in the occurrence and development of nasal polyps. The possible role of mast cells in the formation of nasal polyps and the specific mechanism deserve further study.

Role of mast cells in the generation of a T-helper type 2 dominated anti-helminthic immune response.

Mast cells are long-lived, innate immune cells of the myeloid lineage which are found in peripheral tissues located throughout the body, and positioned at the interface between the host and the environment. Mast cells are found in high concentrations during helminth infection. Using Kitw-sh mast cell deficient mice, a recently published study in Bioscience Reports by Gonzalez et al. (Biosci. Rep., 2018) focused on the role of mast cells in the immune response to infection by the helminth Hymenolepis diminuta. The authors showed that mast cells play a role in the modulation of Th2 immune response characterized by a unique IL-4, IL-5 and IL-13 cytokine profile, as well as subsequent robust worm expulsion during H. diminuta infection. Unlike WT mice which expelled H. diminuta at day 10, Kitw-sh deficient mice displayed delayed worm expulsion (day 14 post infection). Further, a possible role for mast cells in the basal expression of cytokines IL-25, IL-33 and thymic stromal lymphopoietin was described. Deletion of neutrophils in Kitw-sh deficient mice enhanced H. diminuta expulsion, which was accompanied by splenomegaly. However, interactions between mast cells and other innate and adaptive immune cells during helminth infections are yet to be fully clarified. We conclude that the elucidation of mechanisms underlying mast cell interactions with cells of the innate and adaptive immune system during infection by helminths can potentially uncover novel therapeutic applications against inflammatory, autoimmune and neoplastic diseases.

IL-17-positive mast cell infiltration in the lesional skin of lichen planopilaris: Possible role of mast cells in inducing inflammation and dermal fibrosis in cicatricial alopecia.

Lichen planopilaris (LPP) is a primary cicatricial alopecia characterized by the infiltration of lymphocytes in the upper portion of hair follicles. Inflammation around the bulge region of hair follicles induces destruction of hair follicle stem cells and tissue fibrosis, resulting in permanent hair loss. Treatment is still challenging, and the precise pathophysiology of this disorder is unknown. To clarify the pathogenesis of LPP, we performed histological and immunohistochemical analysis on specimens obtained from LPP patients. Formalin-fixed and paraffin-embedded samples were evaluated by staining with haematoxylin and eosin (HE), toluidine blue stain, immunohistochemistry and immunofluorescence. The immunohistochemical analysis demonstrated that CD4-positive T cells preferentially infiltrated into the follicular infundibulum in the LPP lesions. Toluidine blue stain detected a large number of mast cells in the inflammatory lesions of LPP. Interestingly, immunohistochemical analysis demonstrated that the mast cells harboured IL-17A- and IL-23-producing activity and expressed the IL-23 receptor. The number of IL-17A-positive mast cells was significantly higher in the LPP lesions than in normal scalp. Moreover, the IL-17 receptor was expressed exclusively in the follicular epithelial cells in the LPP lesions. These results suggested that mast cells infiltrating hair follicles might play a role in the pathogenesis of LPP via the IL-23/IL-17 axis.

El papel de los mastocitos en la evaluación de la respuesta inflamatoria posoperatoria, al implantar mallas protésicas para la reparación de defectos de la pared abdominal en biomodelos rata Wistar

Objective: The objective of this study was to evaluate the role of mast cells in the postoperative inflammatory response after implantation of prosthetic mesh to repair abdominal wall defects in Wistar rat. Materials and Methods: An abdominal wall defect (30 x 20 mm) was created in the anterior abdominal wall of 25 adult male Wistar rats. The anatomical defect was then repaired with one of the two type’s meshes. Fibroin and monocryl ultrapo prolene meshes. Fibroin meshes were manufactured by weaving its threads, the polypropylene mesh was bought to Johnson & Johnson-Ethicon. After 28 days of implantation Wistar rats were sacrificed and the mesh with abdominal tissue was extracted. Subsequently the samples were treated with histochemical techniques for histological analysis. Results: The study reported adherence to omentum in both types of meshes used, however, the polypropylene mesh showed widely adhesions to colon, slight to intestine and liver, also in a very lower amount, adhesions to omentum. It was found that mast cells were presented in all the studied regions for the polypropylene mesh (dermis, perimysium, and visceral serosa). Discussion: Studies indicate that mast cells and their products such as histamine, serotonin, and others play a key role in controlling local inflammation, wound healing, adhesions, and reactions to foreign bodies in vivo. Conclusion: We can conclude that this study is a good step to show the possible role of mast cells in the abdominal wall repair process.

Increased mast cell degranulation and co-localization of mast cells with the NMDA receptor-1 during healing after Achilles tendon rupture

The role of inflammation and the mechanism of tendon healing after rupture has historically been a matter of controversy. The purpose of the present study is to investigate the role of mast cells and their relation to the NMDA receptor-1 (a glutamate receptor) during healing after Achilles tendon rupture. Eight female Sprague Dawley rats had their right Achilles tendon transected. Three weeks after rupture, histological quantification of mast cell numbers and their state of degranulation was assessed by histochemistry. Co-localization of mast cell tryptase (a mast cell marker) and NMDA receptor-1 was determined by immunofluorescence. The intact left Achilles tendon was used as control. An increased number of mast cells and a higher proportion of degranulated mast cells were found in the healing Achilles tendon compared to the intact. In addition, increased co-localization of mast cell tryptase and NMDA receptor-1 was seen in the areas of myotendinous junction, mid-tendon proper and bone tendon junction of the healing versus the intact tendon. These findings introduce a possible role for mast cells in the healing phase after Achilles tendon rupture.

Mast cells in calcific aortic stenosis

In developed countries, calcific aortic stenosis (CAS) has become the most common acquired valvular disease and reason for aortic valve replacement. It is considered a form of atherosclerosis and, like the latter, of inflammatory origin, with presence in the calcified aortic valves of blood vessels, lymphatics, lymphocytes, plasma cells, histiocytes, and sometimes also of metaplastic bone tissue. This study is aimed at examining the presence of CD117 – positive mast cells in CAS. In 56 examined calcified aortic valves excised by cardiac surgery, mast cells were constantly present as a part of the polymorphous cellular infiltrate; in individual cases, their numbers were 1–90 (median 24). The numbers were significantly higher in the congenitally malformed/bicuspid valves (median 40) than in the tricuspid ones (median 20). In valves with presence of metaplastic bone, mast cells were significantly more numerous (median 42) than in those without metaplasia (median 20). In 12 normal aortic valves obtained at autopsies, the numbers of mast cells were 4–21 (median 11). Discussed is a possible role of mast cells in pathogenesis of CAS.

Possible role of mast cells and IL-37 in the pathogenesis of psoriasis

Possible role of mast cells and IL-37 in the pathogenesis of psoriasis

Significance of mast cell distribution in placental tissue and membranes in spontaneous preterm birth.

BackgroundPreterm birth is a common cause of adverse neonatal and childhood outcomes, in both the short and long term. Preterm labor is commonly associated with inflammation at the maternal–fetal interface. There is some indirect evidence that mast cells (MCs) might represent a link between hormonal influences and local reactions leading to the onset of labor.Patients and methodsThe placentas and membranes of 51 uncomplicated spontaneous term births were compared to those from 50 spontaneous preterm births. Immunohistochemical staining for MC tryptase was undertaken allowing MC concentration, location, and degranulation status to be determined. Regression modeling was used to compare results.ResultsThere were no significant differences in the demographic characteristics of the two cohorts. There were significantly more MCs in the decidua for term births than preterm births (P=0.03). The presence of histological chorioamnionitis did not affect MC concentrations.ConclusionDespite evidence suggesting a possible role for MCs in spontaneous preterm birth, this study found that the concentration of decidual MCs was in fact significantly lower in preterm compared to term birth.

The Possible Role of Mast Cells in the Odontogenic Cyst's Pathogenesis: A Comparative Study between Dentigerous Cyst and Keratocystic Odontogenic Tumor.

Background. Recently, mast cells were recognized in the pathogenesis of more aggressive pathologic lesions. This study was aimed to evaluate and compare the density of mast cells in Dentigerous cyst (DC) and Keratocystic odontogenic tumor (KCOT) regarding their different clinical behavior. Method. This study was conducted on 23 and 26 cases of DC and KCOT, respectively. Four-micron sections were prepared for Toluidine blue staining and mast cell densities in two desired cysts were studied. Final data was analyzed via t-test and Mann-Whitney U test method regarding the significant level lower than 0.05. Results. Mast cell densities were significantly higher in KCOTs for deep and superficial layers and both layers (P < 0.05). The density of degranulated mast cells in the deeper layers and both layers was significantly higher in KCOTs (P < 0.05). However, the density of degranulated mast cells in the superficial layer had no significant difference (P > 0.05). Conclusion. It seems that mast cells may be involved in the pathogenesis of KCOT, but, regarding wide range of mast cell's biologic activities, further investigations are recommended to confirm the issue and prepare the details.

Immunohistochemical Evaluation of Mast Cells in Leukoplakia and Oral Squamous Cell Carcinoma.

More than 90% of oral cancers are squamous cell carcinomas with oral leukoplakia being the most common potentially malignant disorder. Among the cell types in the stroma, mast cells play an important role in tumourigenesis through various mechanisms. The present study was aimed at comparing the mast cell count among normal oral mucosa, leukoplakia and Oral squamous cell carcinoma (OSSC) and to evaluate the possible role of mast cells in carcinogenesis. Mast cell count was assessed immunohistochemically using anti-mast cell tryptase amongst 20 cases of leukoplakia and OSSC each and 10 normal gingival samples. Overall comparison was done using Kruskal Wallis test and intergroup comparison was done using Mann-Whitney U test. The results of the present study showed an increase in mast cell count from normal oral mucosa (Mean: 7.73) to leukoplakia (Mean: 15.11) to squamous cell carcinoma (Mean: 22.73). Comparison of mean number of mast cells amongst three groups (p-value: 0.001) and intergroup comparisons showed statistical significance. Mast cells favour malignant transformation and can be used as indicators of disease progression.

Abstract 2342: Characterization of inflammatory markers and mast cells in association with prostate cancer

Abstract Evidence suggests that there is a strong association between chronic inflammation and prostate cancer development and/or progression. While chronic inflammation is known to serve as an “enabling characteristic” in many cancers, the mechanism whereby it contributes to carcinogenesis and progression is still very controversial. This is particularly true for cells of the innate immune system, such as mast cells, that have been shown to possess both pro- and anti-tumor properties. The role of mast cells in prostate cancer is of particular interest, as evidence suggests that they influence cancer progression and immune modulation. The current study seeks to characterize mast cell density and mast cell-to-epithelial ratio in relation to prostate cancer recurrence using a unique set of tissue microarrays (TMAs) from a case-control study nested in a cohort of prostate cancer patients who underwent radical prostatectomy. These studies are aided by novel digital image analysis using a software framework integrating whole slide imaging, virtual microscopy, and ImageJ based analysis algorithms. Our preliminary results, obtained via analysis of a prostate cancer TMA containing matched cancer and benign tissues from 727 cases of radical prostatectomy patients, correlated with the literature in that the mast cell density (mast cell number/total tissue area) was significantly higher in cancer versus benign (p = 0.0016). We will expanded this study to determine if mast cell number correlates with epithelial area in the same cohort and to examine mast cell density in correlation to the presence, grade, or progression of prostate cancer. Furthermore, we will be examining this in a large full tissue slide cohort in relation to Gleason grade and stage. Finally, we are expanding this study to explore a possible role for mast cells in the racial disparity in prostate cancer incidence and prognosis. Citation Format: Heidi Hempel, Ibrahim Kulac, Nathan S. Cuka, Toby C. Cornish, Elizabeth A. Platz, Angelo M. DeMarzo, Karen S. Sfanos. Characterization of inflammatory markers and mast cells in association with prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2342. doi:10.1158/1538-7445.AM2015-2342

Alpha tryptase allele of Tryptase 1 (TPSAB1) gene associated with Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in Vietnam and Philippines

We previously reported, significantly higher levels of Chymase and Tryptase in early stage plasma of DSS patients prior to the occurrence of shock suggesting a possible role of mast cells in dengue pathogenesis. To further investigate, we analyzed CMA1 promoter SNP (rs1800875) and TPSAB1 gene alleles, which encode the Human Chymase and α- and β- tryptase 1 enzymes respectively, for susceptibility to Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in patients from hospitals in Vietnam (Ho Chi Minh City and Vinh Long) and the Philippines. While the CMA1 promoter SNP (rs1800875) was not associated with DHF/DSS, the homozygous form of α-tryptase allele was associated with DSS patients in Vinh Long and the Philippines (OR=3.52, p<0.0001; OR=3.37, p<0.0001, respectively) and with DHF in Ho Chi Minh City (OR=2.54, p=0.0084). Also, a statistically significant association was observed when DHF and DSS were combined in Vinh Long (OR=1.5, p=0.034) and the Philippines (OR=2.36, p=0.0004); in Ho Chi Minh City when DHF and DSS were combine an association was observed, but it was not statistically significant (OR=1.5, p=0.0505). Therefore, the α-tryptase might have a possible effect on the susceptibility to severe form of Dengue infection.

Quantification and localization of mast cells in periapical lesions.

Background:Periapical lesions occur in response to chronic irritation in periapical tissue, generally resulting from an infected root canal. Specific etiological agents of induction, participating cell population and growth factors associated with maintenance and resolution of periapical lesions are incompletely understood. Among the cells found in periapical lesions, mast cells have been implicated in the inflammatory mechanism.Aim:Quantifications and the possible role played by mast cells in the periapical granuloma and radicular cyst. Hence, this study is to emphasize the presence (localization) and quantification of mast cells in periapical granuloma and radicular cyst.Materials and Methods:A total of 30 cases and out of which 15 of periapical granuloma and 15 radicular cyst, each along with the case details from the previously diagnosed cases in the department of oral pathology were selected for the study. The gender distribution showed male 8 (53.3%) and females 7 (46.7%) in periapical granuloma cases and male 10 (66.7%) and females 5 (33.3%) in radicular cyst cases. The statistical analysis used was unpaired t-test.Results:Mean mast cell count in periapical granuloma subepithelial and deeper connective tissue, was 12.40 (0.99%) and 7.13 (0.83%), respectively. The mean mast cell counts in subepithelial and deeper connective tissue of radicular cyst were 17.64 (1.59%) and 12.06 (1.33%) respectively, which was statistically significant. No statistical significant difference was noted among males and females.Conclusion:Mast cells were more in number in radicular cyst. Based on the concept that mast cells play a critical role in the induction of inflammation, it is logical to use therapeutic agents to alter mast cell function and secretion, to thwart inflammation at its earliest phases. These findings may suggest the possible role of mast cells in the pathogenesis of periapical lesions.

Mast cells: potential positive and negative roles in tumor biology.

Mast cells are immune cells that reside in virtually all vascularized tissues. Upon activation by diverse mechanisms, mast cells can secrete a broad array of biologically active products that either are stored in the cytoplasmic granules of the cells (e.g., histamine, heparin, various proteases) or are produced de novo upon cell stimulation (e.g., prostaglandins, leukotrienes, cytokines, chemokines, and growth factors). Mast cells are best known for their effector functions during anaphylaxis and acute IgE-associated allergic reactions, but they also have been implicated in a wide variety of processes that maintain health or contribute to disease. There has been particular interest in the possible roles of mast cells in tumor biology. In vitro studies have shown that mast cells have the potential to influence many aspects of tumor biology, including tumor development, tumor-induced angiogenesis, and tissue remodeling, and the shaping of adaptive immune responses to tumors. Yet, the actual contributions of mast cells to tumor biology in vivo remain controversial. Here, we review some basic features of mast cell biology with a special emphasis on those relevant to their potential roles in tumors. We discuss how using in vivo tumor models in combination with models in which mast cell function can be modulated has implicated mast cells in the regulation of host responses to tumors. Finally, we summarize data from studies of human tumors that suggest either beneficial or detrimental roles for mast cells in tumors.

EFFECTS OF MAST CELLS ON THE FUNCTION OF ISOLATED HUMAN TENOCYTES

IntroductionTendinopathy, a pathological condition caused by tendon overuse, adversely affects millions of people in athletic and occupational settings worldwide. The underlying molecular mechanisms in the development of tendinopathy are poorly...