• Archives of Pharmacal Research
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• v.27 no.5
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• pp.518-523
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• 2004

An allergic reaction ensues after antigen binds to mast cell or basophil high affinity IgE receptor, Fc$\varepsilon$RI, resulting in degranulation of various inflammatory mediators that produce various allergic symptoms. In this study, i) we isolated the active component for the inhibition of mast cell degranulation from the extract of leaves of Castanea crenata and identified it as quercetin; ii) we established the total synthesis procedure of quercetin; iii) using quercetin as positive control, we excavated some lead compounds that possess inhibitory activities for mast cell degranulation by screening the chemical libraries of 1,3-oxazolidine derivatives prepared by solid phase combinatorial chemistry. Some of 1,3-oxazolidine compounds possessing acetyl and 3',4'-dichlorophenyl group displayed strong inhibitory activities on Fc$\varepsilon$RI-mediated mast cell degranulation, suggesting that they can be used as lead compounds for the development of anti-allergic agents.

• Parasites, Hosts and Diseases
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• v.43 no.1 s.133
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• pp.33-37
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• 2005

Eosinophil degranulation is considered to be a key effector function for the killing of helminthic worms and tissue inflammation at worm-infected lesion sites. However, relatively little data are available with regard to eosinophil response after stimulation with worm-secreted products which contain a large quantity of cysteine proteases. In this study, we attempted to determine whether the degranulation of human eosinophils could be induced by the direct stimulation of the excretory-secretory products (ESP) of Paragonimus westermani, which causes pulmonary paragonimiasis in human beings. Incubation of eosinophils for 3 hr with Paragonimus-secreted products resulted in marked degranulation, as evidenced by the release of eosinophil-derived neurotoxin (EON) in the culture supernatants. Moreover, superoxide anion was produced by eosinophils after stimulation of the ESP. The ESP-induced EDN release was found to be significantly inhibited when the ESP was pretreated with protease inhibitor cocktail or the cysteine protease inhibitor, E-64. These findings suggest that human eosinophils become degranulated in response to P. westermani-secreted proteases, which may contribute to in vivo tissue inflammation around the worms.

• International Journal of Fuzzy Logic and Intelligent Systems
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• v.13 no.4
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• pp.245-253
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• 2013

Knowledge representation realized by information granules is one of the essential facets of granular computing and an area of intensive research. Fuzzy clustering and clustering are general vehicles to realize formation of information granules. Granulation - degranulation paradigm is one of the schemes determining and quantifying functionality and knowledge representation capabilities of information granules. In this study, we augment this paradigm by forming and optimizing a collection of associations among original and transformed information granules. We discuss several transformation schemes and analyze their properties. A series of numeric experiments is provided using which we quantify the improvement of the degranulation mechanisms offered by the optimized transformation of information granules.

• Parasites, Hosts and Diseases
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• v.46 no.2
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• pp.95-99
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• 2008

Eosinophil degranulation plays a crucial role in tissue inflammatory reactions associated with helminth parasitic infections and allergic diseases. Paragonimus westermani, a lung fluke causing human paragonimiasis, secretes a large amount of cysteine proteases, which are involved in nutrient uptake, tissue invasion, and modulation of hos's immune responses. There is, however, limited information about the response of eosinophils to direct stimulation by cysteine proteases (CP) secreted by P. westermani. In the present study, we tested whether degranulation and superoxide production from human eosinophils can be induced by stimulation of the 2 CP (27 kDa and 28 kDa) purified from excretory-secretory products (ESP) of P. westermani newly excysted metacercariae (PwNEM). A large quantity of eosinophil-derived neurotoxin (EDN) was detected in the culture supernatant when human eosinophils isolated from the peripheral blood were incubated with the purified 27 kDa CP. Furthermore, the 27 kDa CP induced superoxide anion production by eosinophils in time- and dose-dependent manners. In contrast, the purified 28 kDa CP did not induce superoxide production and degranulation. These findings suggest that the 27 kDa CP secreted by PwNEM induces superoxide production and degranulation of human eosinophils, which may be involved in eosinophil-mediated tissue inflammatory responses during the larval migration in human paragonimiasis.

• Biomolecules & Therapeutics
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• v.20 no.6
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• pp.526-531
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• 2012

During our on-going studies to identify bioactive compounds in medicinal herbs, we found that saucerneol F (SF), a naturally occurring sesquilignan isolated from Saururus chinensis (S. chinensis), showed in vitro anti-inflammatory activity. In this study, we examined the effects of SF on the generation of 5-lipoxygenase (5-LO) dependent leukotriene $C_4$ ($LTC_4$), cyclooxygenase-2 (COX-2) dependent prostaglandin $D_2$ ($PGD_2$), and on phospholipase $C{\gamma}1$ ($PLC{\gamma}1$)-mediated degranulation in SCF-induced mouse bone marrow-derived mast cells (BMMCs). SF inhibited eicosanoid ($PGD_2$ and $LTC_4$) generation and degranulation dose-dependently. To identify the molecular mechanisms underlying the inhibition of eicosanoid generation and degranulation by SF, we examined the effects of SF on the phosphorylation of $PLC{\gamma}1$, intracellular $Ca^{2+}$ influx, the translocation of cytosolic phospholipase $A_2$ ($cPLA_2$) and 5-LO, and on the phosphorylation of MAP kinases (MAPKs). SF was found to reduce intracellular $Ca^{2+}$ influx by inhibiting $PLC{\gamma}1$ phosphorylation and suppressing the nuclear translocations of $cPLA_2$ and 5-LO via the phosphorylations of MAPKs, including extracellular signal-regulated protein kinase-1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Taken together, these results suggest that SF may be useful for regulating mast cell-mediated inflammatory responses by inhibiting degranulation and eicosanoid generation.

• The Journal of Pediatrics of Korean Medicine
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• v.18 no.2
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• pp.107-117
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• 2004

Objective : Atopic dermatitis has a close relationship with degranulation of mast cell and separation of Histamine. As there's no experiment with herb, using Arctii Fructus, we investigated experimental influence of Arctii Fructus on degranulation of mast cell and separation of histamine in SD rat. Methods : The SD rats are classified into three groups. One group is normal one treated by normal saline before medical treatment. The other is control group prescribed to Compound 48/80 before normal saline treatment. And the third is experimental group prescribed to compound 48/80 after medical treatment of Arctii Fructus. Then, I investigated the experimental results by measuring the degree of degranulation and separation of histamine. The results of investigation on SD rat group showing the degree of inhibitory effect of degranulation of a mast cell are as follow, the normal group treated by normal saline reflecting the degree of degranulation is $6.10{\pm}0.20\;%$, the control group treated by only compound 48/80 is $87.56{\pm}11.00\;%$, the experimental group which treated by compound 48/80 and Arctii Fructus's medical treatment is $16.26{\pm}4.67\;%$. Results : The normal group treated by only normal saline reflecting the degree of degranulation is $6.10{\pm}0.20\;%$, the control group treated by only compound 48/80 is 87.56=11.00 %, the experimental group treated by compound 48/80 and Arctii Fructus's medical treatment is $16.26{\pm}4.67\;%$. This result indicates that the degree of degranulation of mast cell is obviously inhibited (p<0.0l) in the experimental group in comparison with control one. The analysis of data obtained from plasma, which collected from the experimented SDrats' hearts before their death, and the measurement of quantity of histamine secretion show the following results. The quantity of normal group and control one is $25.34{\pm}4.58$ nM, $348.59{\pm}30.77$ nM respectively, and experimental one prescribed to compound 48/80 after medical treatment of Arctii Fructus is $263.56{\pm}21.34$ nM. This result indicates that separation of histamine isobviously inhibited in the experimental group in comparison with control one (p<0.05). Conclusions : Arctii Fructus does obviously inhibit the degree of degranulation of mast cell (p<0.0l) and separation of histamine in the plasma (p<0.05).

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.2
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• pp.213-220
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• 2016

Mast cells are primary mediators of allergic inflammation. Beta-1,3-glucan (BG) protects against infection and shock by activating immune cells. Activation of the BG receptor induces an increase in intracellular $Ca^{2+}$, which may induce exocytosis. However, little is known about the precise mechanisms underlying BG activation of immune cells and the possible role of mitochondria in this process. The present study examined whether BG induced mast cell degranulation, and evaluated the role of calcium transients during mast cell activation. Our investigation focused on the role of the mitochondrial calcium uniporter (MCU) in BG-induced degranulation. Black mouse (C57) bone marrow-derived mast cells were stimulated with $0.5{\mu}g/ml$ BG, $100{\mu}g/ml$ peptidoglycan (PGN), or $10{\mu}M$ A23187 (calcium ionophore), and dynamic changes in cytosolic and mitochondrial calcium and membrane potential were monitored. BG-induced mast cell degranulation occurred in a time-dependent manner, and was significantly reduced under calcium-free conditions. Ruthenium red, a mitochondrial $Ca^{2+}$ uniporter blocker, significantly reduced mast cell degranulation induced by BG, PGN, and A23187. These results suggest that the mitochondrial $Ca^{2+}$ uniporter has an important regulatory role in BG-induced mast cell degranulation.

• IMMUNE NETWORK
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• v.4 no.3
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• pp.176-183
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• 2004

Background: Human seminal plasma (HSP)-induced hypersensitivity is one of the serious complications with sexual intercourse. The clinical manifestations of HSP-induced hypersensitivity may be related to the release of vasoactive mediators from mast cell induced by HSP. It has recently been reported that HSP modulates immune systems and induces mast cell degranulation and histamine release from rat peritoneal mast cells (RPMC). Ketotifen and disodium cromoglycate (DSCG), anti-asthmatic and anti-allergic drugs, have a role of mast cell stabilization and inhibit mast cell-induced leukocyte rolling and adhesion. But the inhibitory agents of HSP-induced mast cell activation are unknown. This study was performed to investigate the effects of DSCG and ketotifen on the HSP-induced mast cell activation. Methods: For this, influences of DSCG and ketotifen on the human seminal plasma-induced degranulation, histamine release and morphological changes of RPMC were observed. Results: The mast cell degranulation and histamine release of RPMC by HSP were induced in a dose-dependent fashion. The HSP-induced cytomorphological changes such as swelling, intracellular vacoules, and interrupted cell boundary were significantly inhibited by pretreatment with DSCG or ketotifen. DSCG and Ketotifen inhibited the HSP-induced degranulation and histamine release from RPMC. Conclusion: From the above results, it is suggested that DSCG and ketotifen have a inhibitory effect of the HSP-induced mast cell activation. DSCG and ketotifen may be used for treatment of HSP-induced hypersensitivity.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.244-244
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• 1994

Cortex Mori, the root bark of mulbery tree has been used as an antiphlogistic, diuretic, and expectorant in herbal medicine. The purpose of this study is to evaluate chicken gamma globulin (CGG)-specific IgE-induced morphologic and functional changes in rat peritoneal mast cells (RPMC), and to determine whether Cortex Mori could inhibit the CGG-specific IgE-depeildent mast cell degranulation and histamine release from RPMC. Results are 1) the degranuration and histamine release from RPMC were not induced within 1 hour after addition of Cortex Mori alone, 2) the CGG and CGG-specific IgE-Induced degranulation from RPMC was observed within 10 minutes, 3) the histamine release from RPMC sensitised with CGG-specific IgE was induced by tile addition of CGG, 4) CGG-specific IgE-dependent degranulation rate in RPMC pretreated with Cortex Mori was significantly Inhibited, compared to that of control group without Cortex Mori pretreatment, and 5) the CGG-specific IgE-dependent histamine release from RPMC was significantly inhibited by pretreatment with Cortex Mori. These data suggest that Cortex Mori contains some substances with capabilities to inhibit CGG-specific IgE-dependent degranulation and histamine release from RPMC.

• The Journal of Pediatrics of Korean Medicine
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• v.18 no.1
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• pp.63-75
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• 2004

Objective: Atopic dermatitis has a close relationship with degranulation of mast cell and separation of histamine. As there was no experiment with herb, using Lithospermum erythrorhizon, We investigated experimental influence of Lithospermum erythrorhizon on degranulation of mast cell and separation of histamine in Sprague-Dawley rats. Methods: The SD rats were classified into three groups. One group was a normal one treated by normal saline before medical treatment. The other was a control group prescribed to Compound 48/80 before normal saline treatment. And the third was a expenimental group prescribed to compound 48/80 after medical treatment of Lithospermum erythrorhizon. Then, We investigated the experimental results by measuring the degree of degranulation and separation of histamine. Results: Lithospermum erythrorhizon did obviously inhibit the degree of degranulation of mast cell(p<0.05). Lithospermum erythrorhizon inhibited the separation of histamine in the plasma. Conclusion: Lithospermum erythrorhizon may be one of the effective therapeutic regimens on atopic dermatitis.