Chymase Mast Cells Research Articles

MASTer cell: chief immune modulator and inductor of antimicrobial immune response.

Mast cells have long been recognized for their involvement in allergic pathology through the immunoglobulin E (IgE)-mediated degranulation mechanism. However, there is growing evidence of other "non-canonical" degranulation mechanisms activated by certain pathogen recognition receptors. Mast cells release several mediators, including histamine, cytokines, chemokines, prostaglandins, and leukotrienes, to initiate and enhance inflammation. The chemical nature of activating stimuli influences receptors, triggering mechanisms for the secretion of formed and new synthesized mediators. Mast cells have more than 30 known surface receptors that activate different pathways for direct and indirect activation by microbes. Different bacterial strains stimulate mast cells through various ligands, initiating the innate immune response, which aids in clearing the bacterial burden. Mast cell interactions with adaptative immune cells also play a crucial role in infections. Recent publications revealed another "non-canonical" degranulation mechanism present in tryptase and chymase mast cells in humans and connective tissue mast cells in mice, occurring through the activation of the Mas-related G protein-coupled receptor (MRGPRX2/b2). This receptor represents a new therapeutic target alongside antibiotic therapy. There is an urgent need to reconsider and redefine the biological role of these MASTer cells of innate immunity, extending beyond their involvement in allergic pathology.

Effect of probiotic on mast cell density and expression of tryptase, chymase, and TNF-α in the urinary bladder of rats with high cholesterol

In this study, it was aimed to immunohistochemically evaluate the possible effect of probiotic supplementation on rats fed a high cholesterol diet on mast cell heterogeneity and density in the urinary bladder and on the expression of chymase, tryptase and tumor necrosis factor-alpha (TNF-α) cytokine in the urinary bladder. Three groups were formed in the study. For 8 weeks, Group 1 (control group) was fed regular rat diet. Food for Group 2 (feeding +2% cholesterol) (high cholestrol group) was provided for 8 weeks. For the last four weeks, Group 3 (%2 cholesterol + Lactobacillus acidophilus) (probiotic group) was administered L. acidophilus probiotics. Levels of total cholesterol (TC) was measured by using a spectrophotometric autoanalyzer. Serum TC levels were remarkably increased in group 2 compared to the group 1 (P<0.05). TC decreased significantly (P <0.05) in group 3 compared to group 2. The number of mast cells in the control group and the probiotic group were close to each other. Only safranin O (SO) (+) mast cells was increased in the probiotic group. While there was no difference between control and high cholesterol groups, an increase in the number of tryptase mast cells was found in the probiotic group. The number of chymase mast cells declined in the probiotic group compared to control and high cholesterol groups. There was no significant difference in TNF-α immunoreactivity between the three groups. In conclusion, in this study, possible effects of cholesterol and probiotics on mast cell heterogeneity and expression of chymase, tryptase, TNF-α were revealed.

Low numbers of tryptase+ and chymase+ mast cells associated with reduced survival and advanced tumor stage in melanoma.

The role of mast cells in cutaneous melanoma remains unclear. Tryptase and chymase are serine proteinases and major proteins in mast cell secretory granules. Therefore, this study aimed to investigate the presence of tryptase and chymase mast cells in benign and malignant cutaneous melanocytic lesions and in lymph node metastases of melanomas. The presence of positively stained mast cells was correlated with clinicopathological characteristics in invasive melanomas. Paraffin-embedded sections of 28 benign (13 intradermal, 10 compound, and five junctional nevi) and 26 dysplastic nevi, 15 in-situ melanomas, 36 superficially (pT1, Breslow's thickness<1 mm), and 49 deeply (pT4, Breslow's thickness>4 mm) invasive melanomas and 30 lymph node metastases were immunohistochemically stained for mast cell tryptase and chymase, and immunopositive cells were counted using the hotspot counting method. The mean count of tryptase and chymase mast cells was lower in invasive melanomas compared with in-situ melanomas and dysplastic and benign nevi. In deeply invasive melanomas, the difference was statistically significant compared with dysplastic nevi (P=0.003 for tryptase and P=0.009 for chymase) and in-situ melanomas (0.043 for tryptase). Low numbers of tryptase mast cells were associated with poor overall survival (P=0.031) in deeply invasive melanomas and with a more advanced stage (T1b, P=0.008) in superficially invasive melanomas. Low numbers of chymase mast cells were associated with microsatellites (P=0.017) in deeply invasive melanomas. The results suggest that these serine proteinases of mast cells may be protective in the pathogenesis of melanoma.

Multimodality treatment of malignant pleural mesothelioma with or without immunotherapy: does it change anything?☆

The purpose of this study was to investigate immunological effector cells and angiogenesis in malignant pleural mesothelioma (MPM) patients, who underwent multimodality treatments. Clinical and pathological characteristics of 57 patients, with International Mesothelioma Interest Group stage II-III MPM, who underwent two different multimodality treatments (with and without immunotherapy) between 1999 and 2008 were analyzed. CD8+, CD4+ and Foxp3+ tumor-infiltrating lymphocytes, tryptase and chymase mast cells (MCs), CD34, number of microvessels and vascular endothelial growth factor were determined by immunohistochemistry. The histology was 51 epitheliomorf and 6 biphasic. The stage was III in 41 cases and II in 16 cases. With an average follow-up of 69 months (range 9-115) 14 patients are still alive and the overall median actuarial survival is 21.4 months. Tryptase MCs, CD8+ and Foxp3+ lymphocytes had significantly increased in the interleukin 2 (IL-2) treated group. Moreover, the number of microvessels was significantly lower in IL-2 treated patients. This study indicates that immunotherapy leads to an increase in cytotoxic CD8+ lymphocytes and tryptase MCs and to a decrease of the tumoral neoangiogenesis. Changes in MPM microenvironment induced by immunotherapy may play a major role in the local control of this disease and need further investigations.

Tryptase Mast Cells in Malignant Pleural Mesothelioma as an Independent Favorable Prognostic Factor

Malignant pleural mesothelioma is a highly aggressive neoplasm with an incidence that is increasing world-wide. Mast cells are part of the innate immune system and have been associated with different solid tumors, but there is controversy surrounding their pro- and antitumorigenic effects in cancers. There are two subsets of human mast cells, resulting from the expression of different enzymes: tryptase positive mast cells and chymase positive mast cells. The purpose of this study was to determine the presence and prognostic significance of tumor infiltrating mast cells in mesothelioma. Tryptase and chymase mast cell counts were determined by immunohistochemistry in 60 patients with mesothelioma. All pathologic samples were from patients who underwent treatment with intrapleural preoperative interleukin-2 (18 x 10(6) IU/d for 3 days). After one day of recovery, patients underwent surgery. Pleural samples were also immunostained for CD34 to evaluate microvessel count. High tryptase mast cells counts were found in the majority (73.3%) of the cases studied, and the results were significantly associated with both overall survival (p = 0.02) and time to progression (p = 0.01). This finding was confirmed using multivariate analysis: a higher tryptase mast cells count emerged as an independent favorable prognostic factor (p = 0.02). However, tryptase mast cells count did not show significant correlation with microvessel count. These results suggest that tumor infiltrating tryptase mast cells, after interleukin-2 preoperative induction therapy, predict improved clinical outcome in patients with malignant pleural mesothelioma, and highlight the critical role of the local inflammatory response in mesothelioma cancer progression.

Enzyme-histochemical Detection of a Chymase-like Proteinase within Bovine Mucosal and Connective Tissue Mast Cells

The presence of chymase-like proteinase in bovine mast cells was investigated by an enzyme-histochemical technique (naphthol-AS-D-chloroacetate as substrate) in normal skin, primary bronchus, lung and duodenum. The counts and distribution of chymase-positive and toluidine blue-positive mast cells were compared by means of successive staining. Mast cells with chymase-like activity were detected in all areas, but their proportion was greater in connective than mucosal tissues, with the exception of the skin. These results contrast with those obtained in rodents, in which chymase-like proteinases are detected in all tissues and also in all mast cells. Bovine mast cells are closer to those of human beings, in which chymase-containing mast cells predominate in connective tissues, including skin. The results suggest that more than one chymase subset is present, at least in duodenum. The possible occurrence of dual-specific chymase mast cells, as in other ruminants, is discussed.