• Journal of Periodontal and Implant Science
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• 제26권2호
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• pp.376-395
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• 1996

The neuropeptide substance P(SP) has been recognized to modulate immune systems, with close proximity between peptidergic sensory nerve endings and immune cells. These include the macrophage and neutrophil activation, IL-2 production in T cell, augmentation of Ig synthesis, mast cell degranulation, $PGE_2$ and collagenase secretion in synoviocytes. In this study I examined SP-induced various biological activities such as antimicrobial action, cytokine production, and mast cell degranulation in the presence or absence of other inflammatory cell activators. Antimicrobial studies showed that undifferentiated HL-60 cells were not affected by SP. However, SP significantly enhanced antimicrobial action of TPA-treated or dbcAMP-treated HL-60 cells which had been differentiated into PMN or macrophage/monocyte. I could not find synergistic relationship between SP and LPS in parallel experiments of the above. SP did not induce IL-l production from murine macrophage cell line RAW264.7 whether costimulated with LPS or not. Mast cell degranulation was occured only when stimulated with high dose ($10^{-5}M$) of SP and the degree of this activation was slightly reduced by simultaneous application of $MIP-1{\alpha}$. In addition, CGRP which is known to be a common coexisting neuropeptide with SP within specific fibers did not augment the function of SP on mast cell degranulation. These results suggest that immunoregulatory activities of SP could be mediated through direct upregulation of various functions of immune cells and also upregulation of responsiveness of immune cells to other immune activators.

• 대한본초학회지
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• 제25권3호
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• pp.35-41
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• 2010

Objectives : Allergy is an immune dysfunction caused by degranulation from mast cells in the early phase of allergic disease including allergic rhinitis (AR). The purpose of this study was to investigate the effects of Osterici Radix, roots of Ostericum koreanum Maximowicz in human mast cells and experimental allergic animal models. Methods : The anti-allergic effect of Osterici Radix water extract (NK-W) was investigated in human mast cell line, HMC-1 cells, and compound 48/80-induced systemic anaphylactic response in rats and ovalbumin (OVA)-induced AR in mice. Animals were orally administrated with NK-W (10 and 50 mg/kg) or anti-histamine drug, dosodium cromoglycate (50 mg/kg), and then intraperitoneally injected with compound 48/80 (8 mg/kg) or sensitized with 0.1% OVA into nasal. Animals were observed plasma histamine and histological changes of nasal mucosa. Also, mast cell degranulation and histamine production were determined in compound 48/80-stimulated HMC-1 cells. Results : NK-W inhibited compound 48/80-induced degranulation of mast cells and histamine releasing in HMC-1 cells. NK-W decreased mortality and serum histamine releasing in compound 48/80-induced anaphylatic rats in a dose-dependently manner. NK-W also inhibited serum histamine levels in OVA-induced AR mice and improved abnormal histological changes such as expansion of grandular cells and hypertrophy of epithelium in the nasal mucosa. These results indicate that Osterici Radix water extract suppress allergic response through downregulation of mast cell activation. Conclusions : This study suggests that a therapeutic potential of Osterici Radix as a source of anti-allergic agents for use in a number of allergic diseases.

• 대한수의학회지
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• 제31권1호
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• pp.77-87
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• 1991

In order to know the influence of mast cells on the mammary tumor development, the growth of the mammary carcinoma, the numerical changes and the morphological findings of mast cells appeared in the tumor were microscopically observed in the rat treated with DMBA and each chemical of histamine, heparin, pyrilamine or cimetidine. The results observed were summarized as follows: The tumor induction time that represented the number of days elapsing between the 3rd DMBA administration until a first tumor became $10{\times}10mm$ in diameter was $42.5{\pm}4.7$ days, and the mean number of tumor mass per rat was $3.4{\pm}1.2$ in the DMBA-treated group. No significant difference was apparent in the tumor induction time of the histamine-treated group, heparin-treated group or pyrilamine-treated group compared with the control group, but in the cimetidine-treated group the tumor induction time was $61.8{\pm}10.6$ days (p<0.005). The mean number of tumors per rat was $2.1{\pm}0.9$ in the cimetidine-treated group in contrast to $3.4{\pm}1.3$ in the control group (p<0.005). Numerical changes of mast cells were observed according to the development of DMBA induced mammary tumors that were separated into three major classes of tumors. The numbers of mast cells in all the experimental group were inclined to increase significantly according to the mammary tumor development (p<0.005), and the histamine-treated group, heparin-treated group, or pyrilamine-treated group were nearly similar to the control group. But the mast cells in the each stage of tumor development were more numerous in the cimetidine-treated group than in the control group (p<0.005). There were not significant in the numerical changes of mast cells among the experimental groups on each stage of carcinomas separated by early stage, middle stage and late stage. In the morphological characteristics of mast cells, the degranulation was not detectable from the hyperplasia stages to the early stage of carcinoma, but its degranulation was observed at the middle stage of carcinoma. Most mast cells were nearly degranulated at the late stage of carcinoma. The histamine treated group, pyrilamine-treated group and cimetidine treated group did not differ from the control group in morphological changes of mast cells, but the degranulation was shown mild in the heparin-treated group. And the degranulation gave rise to the depletion of intercellular matrix via exocytosis all the experimental group. From above results, it is supposed that mast cells inhibit the tumor development and that the inhibition is not caused by a single-factor, but by a complex activities of mast cell mediators.

• Applied Microscopy
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• 제17권1호
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• pp.98-114
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• 1987

Degranulation of the rat peritoneal mast cell induced by intraperitoneal injection of horseradish peroxidase(HRP) was studied using light and electron microscopes. 1. Rat peritoneal mast cells in the Tyrode's buffered salt solution injected control group did not show any particular morphological changes following the specified time course. 2. Under the light microscope, the majority of mast cells observed 10 minutes after HRP injection were nearly the same as those of the control group. However, after 30 minutes, granule densities or staining properties of certain cells began to decrease and these appearances increased gradually until 12 hours after injection, at which time small groups of granules being stained pale-red or pink with toluidine blue were easily identified in the cytoplasm of many cells, and numerous extruded granuleg were scattered around these cells. 3. In the mast cells representing the early stage of degranulation induced by HRP, the electron densities of certain granules decreased as the size enlarged, and perigranular cavities were formed by perigranular membrane expansion. As a result, a thin cytoplasmic septum was formed between the expanded perigranular membrane and the cytoplasmic membrane in the cell periphery, and fusion of the adjacent perigranular membranes was observed in the inner side of the cell. 4. In some mast cells, one or two changes in the peripheral cytoplasmic septum could be seen. One was a focal rupture of the peripheral septum and the other was the formation of a saccule containing one or more vesicles. This saccule was thought to be used for granule-extrusion site and/or material absorptive apparatus judging from the morphological characteristics. 5. As the degranulation proceeded, the granule was extruded from the cell after partial rupture of the peripheral cytoplasmic septum. This phenomenon proceeded to-ward the inner side of the cell through the fused perigranular cavities, and consequently several distinct cavities containing a few unextruded membrane-free granules were formed throughout the cytoplasm after 12 hours. As a rule, the granule-extrusion sites were relatively fewer while the cytoplasmic cavities resulting from degranulation were more numerously observed. Thus, it was thought that the granule-extrusion sites tended to be restricted in the HRP-induced degranulation.

• Biomolecules & Therapeutics
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• 제29권5호
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• pp.492-497
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• 2021

Levels of sphingosine 1-phosphate (S1P), an intercellular signaling molecule, reportedly increase in the bronchoalveolar lavage fluids of patients with asthma. Although the type 4 S1P receptor, S1P₄ has been detected in mast cells, its functions have been poorly investigated in an allergic asthma model in vivo. S1P₄ functions were evaluated following treatment of CYM50358, a selective antagonist of S1P₄, in an ovalbumin-induced allergic asthma model, and antigen-induced degranulation of mast cells. CYM50358 inhibited antigen-induced degranulation in RBL-2H3 mast cells. Eosinophil accumulation and an increase of Th2 cytokine levels were measured in the bronchoalveolar lavage fluid and via the inflammation of the lungs in ovalbumin-induced allergic asthma mice. CYM50358 administration before ovalbumin sensitization and before the antigen challenge strongly inhibited the increase of eosinophils and lymphocytes in the bronchoalveolar lavage fluid. CYM50358 administration inhibited the increase of IL-4 cytokines and serum IgE levels. Histological studies revealed that CYM50358 reduced inflammatory scores and PAS (periodic acid-Schiff)-stained cells in the lungs. The pro-allergic functions of S1P₄ were elucidated using in vitro mast cells and in vivo ovalbumin-induced allergic asthma model experiments. These results suggest that S1P₄ antagonist CYM50358 may have therapeutic potential in the treatment of allergic asthma.

• 한국자원식물학회지
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• 제28권3호
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• pp.321-328
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• 2015

Alpiniae officinarum Rhizoma (the rhizome of Alpinia officinarum Hance, known as lesser galangal), a family of Zingiberaceae, has been used to reduce pain of infection and inflammatory diseases in Asian countries. The present study was focused to evaluate the inhibitory degranulation effect of Alpiniae officinarum Rhizoma extract in RBL-2H3 rat basophilic leukemia cells. Cell viability was measured by MTT assay. RBL-2H3 cells were stimulated by phorbol 12-myristate 13-acetate and calcium ionophore A23187. Mast cell degranulation was analyzed by measuring release of β-hexosaminidase in RBL-2H3 cell. Gene expression was measured by qRT-PCR and signaling molecules were detected by immunoblotting. The Alpiniae officinarum Rhizoma extract suppressed β-hexosaminidase release in dose-dependent manner and inhibited cycloxygenase-2 and tumor necrosis factor-α gene expression. Furthermore, it was found that Alpiniae officinarum Rhizoma extract reduced mitogen-activated protein kinases, especially phosphorylated p38, at 0.75 ㎎/㎖ of Alpiniae officinarum Rhizoma extract concentrations. These data show that Alpiniae officinarum Rhizoma extract has immunosuppressive effect in mast cell induced allergic inflammation.

• 약학회지
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• 제56권1호
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• pp.26-34
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• 2012

Mast cells play an important role in early and late phase allergic reactions through allergen and IgE-dependent release of histamine, proteases, prostaglandins, and several multifunctional cytokines. In this study, we investigated whether Cudrania tricuspidata extract (CTE) suppresses IgE-mediated allergic responses in mast cells, an allergic animal model, and its mechanism of action in mast cells. We found that CTE inhibited IgE-mediated degranulation and cytokine production in rat basophilic leukemia (RBL)-2H3 mast cells and bone marrow-derived mast cells (BMMC), as well as passive cutaneous anaphylaxis (PCA) in mice. With regard to its mechanism of action, CTE suppressed the activating phosphorylation of spleen tyrosine kinase (Syk), a key enzyme in mast cell signaling processes and that of LAT, a downstream adaptor molecule of Syk in $Fc{\varepsilon}RI$-mediated signal pathways. CTE also suppressed the activating phosphorylation of mitogen-activated protein (MAP) kinases and Akt. The present results strongly suggest that the anti-allergic activity of CTE is mediated through inhibiting degranulation and allergic cytokine secretion by inhibition of Syk kinase in mast cells. Therefore, CTE may be useful for the treatment of allergic diseases.

• 대한본초학회지
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• 제30권3호
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• pp.1-12
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• 2015

Objectives : In this study, we investigated the effects of Agastachis Herba water (AH-W) extract on compound 48/80-induced mast cell degranulation and histamine release in human mast cells and also anti-asthmatic effect of AH-W extract on ovalbumin (OVA)-induced asthma in mice. Methods : Human mast cells, HMC-1 were treated with AH-W extract in the presence or absence of compound 48/80 (C48/80). Mast cell degranulation was observed by microscope, and the histamine release was measured in culture medium by ELISA. For preparation of asthmatic in vivo model, mice were sensitized (0, 7, and 14 days) with OVA and airway challenged (21, 23, 25, 27, and 29 days). AH-W extract at doses of 100 and 300 mg/kg/body weight was orally administered during OVA challenge once per a day. The levels of immunoglobulin (Ig) E, and Th1/Th2 cytokines, IFN-$\gamma$ and IL-4 were measured in the sera of mice by ELISA. The histopathological change of lung tissues was observed by hematoxylin and eosin (H&E) and Periodic Acid Schiff (PAS) staining. Results : The treatment of AH-W extract significantly decreased the mast cell degranulation and histamine release in C48/80-stimulated HMC-1 cells. In addition, The administration of AH-W extract at does of 100 and 300 mg/kg significantly decreased the serum levels of OVA-specific IgE compared with those of OVA control group. In H&E and PAS staining, AH-W extract inhibited OVA-induced airway inflammation, and inflammatory cells infiltration, and also histopathological damages on lung tissues such as bronchiole epithelial desquamation, goblet cells hyperplasia, and mucin releasing. Conclusions : These results indicate that AH-W extract may improve asthmatic symptoms through mast cell stabilization and inhibiting the lung inflammation in bronchial asthma.

• 한방안이비인후피부과학회지
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• 제14권2호
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• pp.231-241
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• 2001

Mahwang-Shin-Gung-San has been found inhibiting the mast cell-mediated anaphylactic reaction. This report describes an inhibitory effect of Mahwang-Shin-Gung-San (MSGS) on the immediate-type cutaneous allergic reactions. MSGS has concentration -dependently inhibited the ear swelling response induced by compound 48/80 in mouse by intradermal injection. The mast cells in mouse ear tissue undergone ear-swelling response by compound 48/80 were stained by alcian blue/nuclear fast red. MSGS significantly inhibited the compound 48/80-induced degranulation from mast cells in ear tissue. MSGS concentration-dependently inhibited the histamine release from the rat peritoneal mast cells (RPMC) by compound 48/80. We also studied the effect of MSGS on mast cell-dependent passive cutaneous anaphylaxis (PCA) activated by dinitrophenyl IgE antibody. MSGS showed potent inhibition of PCA by oral administration. These results indicate that MSGS inhibits immediate-type allergic reactions by inhibition of mast cell degranulation in vivo and in vitro.

• The Korean Journal of Physiology and Pharmacology
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• 제25권3호
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• pp.251-258
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• 2021

Flos magnoliae (FM), the dry flower buds of Magnolia officinalis or its related species, is a traditional herbal medicine commonly used in Asia for symptomatic relief of and treating allergic rhinitis, headache, and sinusitis. Although several studies have reported the effects of FM on store-operated calcium entry (SOCE) via the ORAI1 channel, which is essential during intracellular calcium signaling cascade generation for T cell activation and mast cell degranulation, the effects of its isolated constituents on SOCE remain unidentified. Therefore, we investigated which of the five major constituents of 30% ethanoic FM (vanillic acid, tiliroside, eudesmin, magnolin, and fargesin) inhibit SOCE and their physiological effects on immune cells. The conventional whole-cell patch clamp results showed that fargesin, magnolin, and eudesmin significantly inhibited SOCE and thus human primary CD4+ T lymphocyte proliferation, as well as allergen-induced histamine release in mast cells. Among them, fargesin demonstrated the most potent inhibitory effects not only on ORAI1 (IC50 = 12.46 ± 1.300 μM) but also on T-cell proliferation (by 87.74% ± 1.835%) and mast cell degranulation (by 20.11% ± 5.366%) at 100 μM. Our findings suggest that fargesin can be a promising candidate for the development of therapeutic drugs to treat allergic diseases.