Mast Cells In Lesions Research Articles

Evidence of IL-17-secreting mast cells in scalp lesions of folliculitis decalvans points to new therapeutic targets in recalcitrant lesions.

Folliculitis decalvans (FD) is a chronic neutrophilic scarring alopecia which exact pathogenesis remains unknown. The recent report on the successful use of a novel anti-IL17 biologic agent in FD and the presence of IL-17-secreting mast cells in other types of scarring alopecias point to a distinct pathogenic mechanism in this disease. Our aim was to study and correlate the expression of IL-17 and mast cells in lesional and non-lesional FD scalp, using immunohistochemical techniques. Increased expression in IL-17 and mast cells was found in lesional scalp compared to non-lesional scalp areas (p<.05). A significant positive correlation between IL-17 and Mast cell Tryptase immunolabeling in non-lesional scalp (r=.64) highlights the role of IL-17-secreting mast cells in "normal-appearing" sites of FD. These findings suggest that targeting both IL-17 and mast cells may be potentially beneficial to better control the chronic inflammatory status of the disease specially in recalcitrant cases of FD.

CD4+CCR5+ T cells and CCL3+ mast cells are increased in the skin of patients with chronic spontaneous urticaria.

The proximity of activated T cells and mast cells in the lesional skin of patients with chronic spontaneous urticaria (CSU) is held to contribute to the development of wheals and angioedema. In a previous study, we demonstrated that increased IL-17 expression in T cells and mast cells in skin lesions of patients with CSU is associated with T/mast cell proximity, but the mechanisms that drive T cell/mast cell co-localization remain unknown. To assess if chemokines expressed in lesional CSU skin contribute to T cell/mast cell proximity. Biopsies from lesional CSU skin were compared to biopsies from healthy skin for expression of CCR5 and its ligand CCL3 by CD4+ T cells and mast cells, respectively. Numbers of CCR5-positive CD4+ T cells in lesional CSU skin were significantly increased as compared to healthy normal skin (p < 0.0001). The number of mast cells expressing CCL3 (ligand for CCR5) in CSU skin was also increased (p < 0.0002) and significant association with T-cell close proximity (p < 0.0001) is noticed. The close proximity of T cells and mast cells in the skin of severe CSU may be driven, at least in part by increased CCR5 and CCL3 expression. Therapies that target CCL3 interaction with CCR5 should be assessed for their effects in CSU.

Acupoint Autohemotherapy Attenuates DNCB-Induced Atopic Dermatitis and Activates Regulatory T Cells in BALB/c Mice.

Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in terms of therapeutic efficacy and mechanism of action is still largely unknown. This study aimed to evaluate the therapeutic efficacies and action mechanisms of intramuscular injections of autologous whole blood (AWB) and mouse immunoglobulin G (IgG) (autologous or heterologous) at acupoints on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse models. Serum levels of total immunoglobulin E (IgE), IgG, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) were measured, as well as mRNA expression levels of Forkhead box P3 (FoxP3), IL-10 and IFN-γ in dorsal skin lesions, and IL-10+, IFN-γ+ and FoxP3+CD4+T cells in murine spleen. It showed that repeated acupoint injection of AWB, autologous total IgG (purified from autologous blood in AD mice) or heterologous total IgG (purified from healthy blood in normal mice) effectively reduced the severity of AD symptoms and decreased epidermal and dermal thickness as well as mast cells in skin lesions. Additionally, AWB acupoint injection was found to upregulate FoxP3+, IL-10+ and IFN-γ+ CD4+T cells in murine spleen, suppressing the production of IgE antibodies and increasing that of IgG antibodies in the serum. Furthermore, both AWB and autologous total IgG administrations significantly elevated FoxP3 expression, mRNA levels of IL-10 and IFN-γ in dorsal skin lesions. However, acupoint injection of heterologous total IgG had no effect on regulatory T (Treg) and Th1 cells modulation. These findings suggest that the therapeutic effects of A-AHT on AD are mediated by IgG-induced activation of Treg cells.

Ixekizumab-induced urticaria is associated with the short duration of remission in psoriasis by activation of mast cells

BackgroundMast cell degranulation plays a pivotal role in urticaria and is also an early histological characteristic of psoriasis. However, whether the activation of mast cells contributes to psoriasis recurrence after discontinuation of IL-17A blockers remains unclear. ObjectiveTo investigate the role of mast cells in ixekizumab treatment-associated urticaria (ITAUR) and assess the effect of urticaria eruption on psoriasis relapse. MethodsA retrospective analysis was performed on biopsies of patients who experienced psoriasis relapse after discontinuation of ixekizumab. Transcriptomic and histopathological features were assessed. Patterns were compared between patients with ITAUR and non-urticaria (NUR) as well as psoriasis-like mice with mast cell activation or inactivation. ResultsPatients with ITAUR experienced early relapse compared to NUR group after treatment withdrawal. Transcriptomic and histopathological analyses revealed that patients with ITAUR had an elevated proportion of mast cells in resolved skin. Especially, the proportion of IL-17A-positive mast cells was inversely correlated with the duration of remission. LimitationsThe mechanism of mast cell activation in ITAUR has not been precisely elucidated. ConclusionIxekizumab treatment increases IL-17A-positive mast cells in lesions of ITAUR, which is associated with early psoriasis relapse after ixekizumab withdrawal.

Evaluation of Mast Cell Density in Mucoepidermoid Carcinoma and Pleomorphic Adenoma.

Mast cells are round to elliptical cells that originate from bone marrow stem cells and enter the peripheral blood. By releasing inflammatory mediators, these cells are involved in type I hypersensitivity, wound healing, defense against pathogens, increased blood vessel formation, and destruction of the extracellular matrix. There are contradictory results regarding the role of mast cells in tumor lesions. Considering the contradictory results and few studies on the density of mast cells in salivary tumors, the present study investigated and compared the density of mast cells in two common salivary gland tumors. In the cross-sectional study after reviewing the records of patients referred to the Pathology Department of the School of Dentistry and Shahid Sadoughi Hospital in Yazd, 15 blocks of each of the mucoepidermoid carcinoma and pleomorphic adenoma tumors were taken. After Giemsa staining of the samples, the average of stained cells in 10 random fields under 400× magnification was counted. The results were analyzed using statistical tests of t-test, ANOVA, Chi-square, and Mann-Whitney in SPSS ver. 22. The average mast cell counts in pleomorphic adenoma (4.2) was higher than muco-epidermoid carcinoma (1.7) but there was no significant relationship (p= 0.305). In mucoepidermoid carcinoma, the numbers of mast cells increased with increasing tumor grade (low: 0/467 moderate: 1/567 high: 2/983) and there was a significant relationship (p= 0.009). According to the results of the present study, it seems that the mast cells accumulation may be secondarily associated with inflammatory responses due to cell accumulation and tissue destruction by tumor cells.

Quantification of mast cells in oral reactive lesions - an immunohistochemical study.

Reactive lesions (RLs) are the most common oral mucosal lesions that are benign in nature and are more likely to reoccur if the lesion or local irritants at the site are not completely removed. The histopathology is usually determined by the stage of the lesion, which includes neovascularization, inflammation, and fibrosis etc. Aim: To evaluate and compare mast cell counts in different reactive lesions with normal gingiva (NG) and to determine the correlation between mast cell count and inflammation, fibrosis, and angiogenesis using immunohistochemistry. 10 pyogenic granulomas (early and late), 10 irritational fibromas, 5 inflammatory fibrous hyperplasia, and 5 peripheral cemento-ossifying fibromas 5 normal gingiva were evaluated. Mast cell counts were compared. ANOVA and t-tests were used to analyze the data. Spearman correlation was used to compare the mast cell count to the inflammation, fibrosis, and vascular components. A p-value of 0.05 was considered statistically significant. The mean number of mast cells were increased in oral reactive lesions when compared to NG. Although mast cells were significantly higher in IFH and IF, there was no correlation found among mast cells and fibrosis/inflammation/vascularity. Reactive process involves multiple interactions among mast cells, endothelial cells, fibroblasts, and other immune cells, among which the role of mast cells has been evaluated. Mast cell count increases in these reactive lesions, possibly reflecting an important role in microenvironment modification, but it is not the sole cause of these lesions' pathogenesis.

Efficacy of Csaba stain to demonstrate mature and immature mast cells in oral inflammatory lesions: An in-vitro study.

Mast cells (MCs) are immune cells of the myeloid lineage and are present in connective tissues throughout the body. Mastocytosis regulates many physiologic processes and affects the pathogenesis of allergic conditions, anaphylactic reactions, autoimmune disorders and leukemias. Toluidine blue is commonly employed as a special stain for MCs that uniformly imparts blue color to both immature and mature cells. Csaba stain that distinguishes mature from immature MCs has not been widely explored. However, its use in differentiating mature and immature cells has not been reported in the literature. The identification of mature and immature MCs may provide a major clue for the diagnosis of any unrecognized systemic pathologies. To evaluate the staining efficacy of Csaba stain, toluidine blue and Leishman's stains in the identification of MCsTo compare the effectiveness of Csaba stain, toluidine blue and Leishman's stains to identify MCs in inflammatory pathologic lesions. Fifty sections of inflammatory lesions were subjected to Csaba stain, toluidine blue and Leishman's stains each for studying MCs. The staining efficacy of the three stains was compared for parameters such as homogeneity, specificity, staining intensity, granular staining property and differentiation between mature and immature cells. The Csaba, toluidine blue and Leishman's stains showed statistically insignificant P = 0.50, 0.95, 0.29, 0.48 for homogeneity, specificity, staining intensity and granular staining property respectively, but Csaba stain showed statistically significant P = 0.0001* in differentiating mature from immature cells. Csaba stain is more effective in differentiating mature from immature MCs compared to the other special stains.

Glycyrrhizic acid suppresses atopic dermatitis-like symptoms by regulating the immune balance.

Glycyrrhiza is one of the most widely used traditional Chinese medicines in China. Its main bioactive ingredient glycyrrhizic acid (GA) has the potential to be used as a treatment for atopic dermatitis (AD) because it has similar actions to steroids, but with relatively few side effects. The objective of this study was to explore the potential mechanisms of GA on AD mice model. Calcipotriol, a vitamin D3 analogue (MC903) was applied topically to establish AD mouse model. Mice were intraperitoneally administrated with 2mg/kg dexamethasone (DEX), 25 or 50 mg/kg GA for 15 days. After mice were executed, skin tissues were collected and detected the expression levels of IL-4, IFN-γ, TNF-α and thymic stromal lymphopoietin (TSLP). The percentages of Th1, Th2, Th17, langerhans cells (LCs) in draining lymph nodes (dLNs) were measured by flow cytometry. Our data demonstrated that GA improved the symptoms of AD by exerting anti-inflammatory and anti-allergic functions in vivo. We found that GA treatment decreased the level of total IgE in serum, suppressed ear swelling, reduced the infiltration of mast cells in skin lesions and decreased expressions of IL-4, IFN-γ, TNF-α and TSLP in skin lesions. Furthermore, our experimental results demonstrated that GA suppressed the Th1/Th2/Th17-immune responses in the dLNs, inhibited the migration of LCs in dLNs. In conclusion, our findings suggested potential therapeutic effects of GA against MC903-induced AD-like skin lesions in mice.

Jiu-Wei-Yong-An Formula suppresses JAK1/STAT3 and MAPK signaling alleviates atopic dermatitis-like skin lesions

Ethnopharmacological relevanceJiu-Wei-Yong-An (JWYA) formula is a traditional Chinese medicine (TCM) prescription used to treat atopic dermatitis (AD) in the clinic. JWYA is considered to have anti-inflammatory and antipruritic properties. However, the mechanism of JWYA remains unclear.Aim of the study: This study aimed to investigate the effect of JWYA on an experimental mouse AD model. Materials and methodsMice were sensitized with 2,4-dinitrochlorobenzene (DNCB) and intragastrically administered with JWYA for 14 days. The therapeutic effect was assessed using a grade four dermatitis score, skin moisture, thickness measurements, and a mouse behavior tests. H&E and toluidine blue staining were used to observe epidermal inflammatory thickening and mast cells in mouse skin lesions. Serum IgE levels and skin TNF-α and IL-4 levels were determined using ELISAs. The TNF-α, IL-1β, IL-4, IL-13, IL-31, IL-33, and IFN-γ mRNA expression levels in skin lesions were detected using qPCR. Network pharmacology analysis based on serum active components was performed to elucidate the mechanism, and the results were verified by Western blotting. Finally, we tested the binding affinity between the active ingredients of JWYA and JAK1 via molecular docking. ResultsJWYA improved the skin lesions of AD mice, relieved itching and reduced skin thickening. Additionally, JWYA decreased the serum IgE level and the levels of TNF-α, IL-1β, IL-4, IL-13, IL-31, IL-33, and IFN-γ in skin. Moreover, JWYA inhibited the activation of JAK1/STAT3 and MAPK (p38, ERK, and JNK) signaling. Molecular docking showed that kaempferol, luteolin, and forsythin have high affinity for JAK1. ConclusionsJWYA alleviates AD-like skin lesions and inhibited inflammation and skin itch. The effect of JWYA is attributed to blocking the JAK1/STAT3 and MAPK signaling pathways. We suggest that JWYA may be an alternative therapy for the treatment of AD.

Therapeutic effects of myricetin on atopic dermatitis in vivo and in vitro

BackgroundMyricetin (Myr) is a flavonoid compound that exist widely in many natural plants. Myr has been proven to have multiple biological functions, including immunomodulatory and anti-inflammatory effects. PurposeIn this study, we investigated the therapeutic effect of Myr on calcipotriol (MC903) induced atopic dermatitis (AD) mouse model and tumor necrosis factor (TNF)-α/interferon (IFN)-γ stimulated human immortal keratinocyte line (HaCaT) in vivo and in vitro. MethodsMC903 was applied topically to the left ears of mice to establish AD mouse model. After the AD model established successfully, the cream base, dexamethasone (DEX) cream or Myr cream were applied on the lesions of mice for 8 days. Through measuring ear thickness and scoring dermatitis severity, we evaluated the therapeutic effect of Myr, the draining lymph nodes (DLNs) and ears of the mice were collected for mechanistic study. In addition, TNF-α and IFN-γ-activated HaCaT cells were used to investigate the underlying mechanism. ResultsOur data demonstrated that Myr alleviated the symptoms of AD by exerting anti-inflammatory and anti-allergic functions in vivo. We found that Myr treatment suppressed ear swelling and IgE level in the serum, reduced the infiltration of mast cells in skin lesions, decreased expressions of thymus and activation regulated chemokine (TARC), IL-4, IFN-γ and thymic stromal lymphopoietin (TSLP) in ear lesions, increased the expressions of filaggrin (FLG). Furthermore, our experimental results demonstrated that Myr down-regulated the mRNA expressions of T-bet and GATA-3 in DLNs. In vitro, Myr treatment decreased MDC and TARC expressions in IFN-γ and TNF-α-induced HaCaT cells by blocking the NF-κB and STAT1 signal pathway. ConclusionThe present study is the first to investigate the anti-atopic effects of Myr. Our findings suggested the therapeutic effects of Myr against MC903-induced AD-like skin lesions in mice. Therefore, Myr may be a potential therapeutic agent for AD.

Autocrine/Paracrine Loop Between SCF+/c-Kit+ Mast Cells Promotes Cutaneous Melanoma Progression.

c-Kit, or mast/stem cell growth factor receptor Kit, is a tyrosine kinase receptor structurally analogous to the colony-stimulating factor-1 (CSF-1) and platelet-derived growth factor (PDGF) CSF-1/PDGF receptor Tyr-subfamily. It binds the cytokine KITLG/SCF to regulate cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and it plays an essential role in melanogenesis. SCF and c-Kit are biologically active as membrane-bound and soluble forms. They can be expressed by tumor cells and cells of the microenvironment playing a crucial role in tumor development, progression, and relapses. To date, few investigations have concerned the role of SCF+/c-Kit+ mast cells in normal, premalignant, and malignant skin lesions that resemble steps of malignant melanoma progression. In this study, by immunolabeling reactions, we demonstrated that in melanoma lesions, SCF and c-Kit were expressed in mast cells and released by themselves, suggesting an autocrine/paracrine loop might be implicated in regulatory mechanisms of neoangiogenesis and tumor progression in human melanoma.

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&amp;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.

Contemporary Updates on the Role of Mast Cells in Oral Lesions: A Review

Mast cell (MCs) is considered the immune cell of myeloid lineage and make a crucial role in the inflammatory process in several types of oral diseases. This mast cell contains 50–200 large granules which are inflammatory mediators, including rich in histamine and heparin. It is mainly found in the connective tissues of the oral mucosa like nerves, blood vessels, and subepithelial areas of the human body. These cells have a key role in the maintenance of many physiologic functions of the body and thus their number was altered in various pathophysiologic diseases of the oral cavity such as benign and malignant tumors, reactive lesions, autoimmune diseases, odontogenic cyst, tumors, etc. The present paper is focused on the current concept and updates on the role and function of mast cells in physiologic and pathologic conditions of the oral cavity.

Quantification of mast cells in nonreactive and reactive lesions of gingiva: A comparative study using toluidine blue and immunohistochemical marker mast cell tryptase.

Background:Mast cells (MCs) are immune cells derived from a multipotent CD34 precursor. The most significant identifying feature of MCs is the presence of metachromatic granules. MCs are increased in oral reactive lesions and are possibly involved in pathogenesis of these lesions.Objectives:1. To compare the number of MCs between reactive and nonreactive lesions of gingiva using toluidine blue (TB) and mast cell tryptase (MCT) as a specific marker for MCs 2. To compare the staining specificity/efficacy of TB and MCT.Methodology:The study sample comprised 90 tissues which were divided into three groups: Group A comprised 30 cases of pyogenic granuloma (PG), Group B consisted of 30 cases of gingival hyperplasia (GH) and Group C comprised 30 cases of pericoronitis. Staining was done between 1% TB and immunohistochemistry (IHC) marker MCT.Results:A significant increase in number of MCs was observed in PG as compared to GH and pericoronitis. IHC marker MCT proved to be a more specific marker for MCs compared to TB.Conclusion:IHC marker MCT is a specific marker compared to TB. The position of MCs changed from juxtaepithelial in GH to deeper connective tissue in PG which was in correlation with the proliferating tissue that is epithelium in GH and blood vessel in PG.

Quantification and distribution of mast cells in oral periapical inflammatory lesions.

Background:Periapical granuloma and periapical cysts develop as a sequela of inflammation of dental pulp, usually a consequence of an infected root canal. Mast cells (MCs) have most frequently been implicated in the pathophysiology of periapical lesions such as periapical granulomas and cysts.Aims:The present study was undertaken to emphasize the presence and quantification of MCs in periapical lesions (granulomas and cysts) using toluidine blue stain, with an aim to elucidate their role in the pathogenesis of these lesions.Materials and Methods:The study comprised a total of 55 previously diagnosed cases (30 cases of radicular cyst and 25 cases of periapical granuloma) selected from the departmental archives. The MCs were quantified in all the sections in the three zones, namely the epithelial, subepithelial, and deeper connective tissue zones. The results were sent for statistical analysis.Statistical Analysis:Wilcoxon paired t-test and Mann–Whitney U test were applied for intra- and intergroup comparison MCs in different zones of periapical granulomas and radicular cyst, respectively.Results:A statistically significant difference was observed between the two lesions in all the three zones, i.e., epithelial, subepithelial, and in deeper connective tissue zone with P = 0.001.Conclusion:Although MCs were present in all the three zones of both periapical cysts and granuloma, they were predominantly observed in radicular cysts than in periapical granuloma. This suggests a significant role of MC in initiation, development, and progression of these periapical lesions.

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.

Mast Cells as Potential Accelerators of Human Atherosclerosis—From Early to Late Lesions

Mast cells are present in atherosclerotic lesions throughout their progression. The process of atherogenesis itself is characterized by infiltration and retention of cholesterol-containing blood-derived low-density lipoprotein (LDL) particles in the intimal layer of the arterial wall, where the particles become modified and ingested by macrophages, resulting in the formation of cholesterol-filled foam cells. Provided the blood-derived high-density lipoproteins (HDL) particles are able to efficiently carry cholesterol from the foam cells back to the circulation, the early lesions may stay stable or even disappear. However, the modified LDL particles also trigger a permanent local inflammatory reaction characterized by the presence of activated macrophages, T cells, and mast cells, which drive lesion progression. Then, the HDL particles become modified and unable to remove cholesterol from the foam cells. Ultimately, the aging foam cells die and form a necrotic lipid core. In such advanced lesions, the lipid core is separated from the circulating blood by a collagenous cap, which may become thin and fragile and susceptible to rupture, so causing an acute atherothrombotic event. Regarding the potential contribution of mast cells in the initiation and progression of atherosclerotic lesions, immunohistochemical studies in autopsied human subjects and studies in cell culture systems and in atherosclerotic mouse models have collectively provided evidence that the compounds released by activated mast cells may promote atherogenesis at various steps along the path of lesion development. This review focuses on the presence of activated mast cells in human atherosclerotic lesions. Moreover, some of the molecular mechanisms potentially governing activation and effector functions of mast cells in such lesions are presented and discussed.

The role of tumour infiltrating mast cells (TIM) in gastric carcinoma remains an enigma : Clinicopathological correlation of mast cell density

Background: Tumour infiltrating mast cells (TIM) may have pro-tumorigenic and anti-tumorigenic roles based on the mediators released and the outcome of that balance at any given stage could determine the net effect on the progression of the cancer.Their pro-tumorigenic role has been documented in many cancers including prostatic cancer and a beneficial role in breast cancer. Their exact role in gastric cancer is still not very clear. Hence the present study was undertaken to make an attempt to infer the role of tumour infiltrating mast cells in gastric carcinoma by measuring mast cell density and correlating with clinicopathological parameters. Methods: Tissue from fifty one cases of gastric carcinoma were analysed and routine histological findings were recorded. Mast cells were clearly demonstrated in tissue using Toluidine Blue stain at pH 2.3. Mast cells were counted in the tumour tissue using an eyepiece grid and expressed as no. of cells / per sq. mm, i.e., mast cell density (MCD). Statistical correlation of the mean Mast cell density (MCD) to clinical parameters like age, gender, location of lesion and pathological parameters like histologic type, grade, depth of invasion, lymph node status were analysed for statistical significance. Results: MCD was statistically significantly higher (Mean MCD +/- S.D:3.48 +/- 2.31) in patient group above 60 years of age compared to patient group below 60 years. MCDwas statistically significantly increased in well differentiated adenocarcinoma (Mean MCD +/- S.D: 7.2 +/- 3.55) stomach compared to moderately differentiated adenocarcinoma and poorly differentiated adenocarcinoma. However, no significant difference in MCD was observed in primary gastric tumour tissue in cases with metastatic deposits in regional lymph nodes and cases without lymph node metastasis. Conclusions: Our results indicate that the role of mast cells in gastric carcinoma could be pro-tumorigenic in the early stages especially during angiogenesis with an increase in MCD in well differentiated tumours and a relative decrease of mast cells in higher histological grades. The absence of any significant difference of MCD in lymph node positive (for metastatic deposit) and lymph node negative group may indirectly indicate no significant role in later stages of the cancer. These results indirectly show that a balance between pro-tumorigenic and anti-tumorigenic factors is involved in the pathogenesis and progression of gastric carcinoma. The role of mast cells in inflammatory and ulcerative gastric lesions which could be precursor lesions to gastric carcinoma also needs to be considered.

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

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

Quantification of mast cells in reactive oral lesions – A clue to the morphologic diversity

OBJECTIVE: Inflammatory fibrous hyperplasia (IFH), pyogenic granuloma (PG), peripheral ossifying fibroma (POF), and peripheral giant cell granuloma (PGCG) are common oral soft-tissue reactive lesions that correspond to excessive connective tissue proliferation as a reaction to trauma or irritational factors local to the oral cavity. These lesions have specific differences in their histopathologic appearances and behavior in spite of having common etiologic factors. Mast cells (MCs) are immune-regulatory cells that have an important role to play in oral inflammation and have also been associated with tissue remodeling and fibrosis in various disorders. METHODOLOGY: MCs were stained with toluidine blue in cases of IFH (20), PG (20), PGCG (20), and POF (20) along with normal gingiva tissue as control (5) for quantification and comparison among them. RESULTS: The mast cell count was low in normal mucosa but a progressive increase was seen from PGCG to IFH to POF with maximum mast cells were evident in PG. There was a significant difference noted in the MC counts between the normal mucosa and the oral reactive lesions (P CONCLUSION: MCs emerged as significant players in the pathogenesis and histopathologic diversity of oral reactive lesions by their effects on fibroblasts and endothelial cells.