1.Comparison of basophil histamine releasability between atopic and nonatopic thmatics.
Jee Woong SON ; Yoon Keun KIM ; Jae Won CHUNG ; Sang Rok LEE ; Sang Heon CHO ; Kyung Up MIN ; Young Yull KOH ; You Young KIM
Journal of Korean Medical Science 1999;14(2):153-158
To compare the mediator releasability between atopic and nonatopic asthmatics, we measured basophil histamine releasability (BaHR) using a calcium-ionophore A23187 and anti-IgE in 137 subjects who were treated at Seoul National University Hospital. Subjects were categorized into atopic (group AA, n=77) or nonatopic asthmatics (group NA, n=32), or normal controls (group NC, n=28). Serum total IgE levels were determined and correlation with BaHR was assessed. Anti-IgE-induced maximal BaHR in groups AA, NA, and NC was 41.0+/-3.2, 23.1+/-4.5, and 16.8+/-3.8, respectively (mean+/-SE, %). Anti-IgE-induced BaHR in group AA was significantly higher than that in groups NA and NC (p<0.05). Calcium ionophore A23187-induced maximal BaHR was 43.1+/-2.8, 40.8+/-4.4, and 50.5+/-5.2, respectively (mean+/-SE, %), and there was no significant difference among the groups. Serum total IgE level correlated significantly with anti-IgE-induced maximal BaHR (r=0.281, p<0.01) but not with that induced by calcium ionophore A23187. In conclusion, IgE receptor-related BaHR is higher in atopic asthmatics than in nonatopic asthmatics, and this increased BaHR in atopics is significantly associated with increased serum total IgE level.
Asthma/immunology*
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Basophils/immunology*
;
Basophils/drug effects
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Calcimycin/pharmacology
;
Child
;
Comparative Study
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Histamine Release/immunology*
;
Histamine Release/drug effects
;
Human
;
IgE/immunology*
;
IgE/blood
;
Ionophores/pharmacology
2.Experimental study of suspicious sensitization component screening on Huachansu injection.
Ying XIAO ; Yu-Bin ZHAO ; Yan-Ming XIE
China Journal of Chinese Materia Medica 2012;37(18):2824-2827
OBJECTIVETo explore a new experimental method for screening of allergens in post-market traditional Chinese medicine injections by confirming allergens in Huachansu injection.
METHODFirst of all, the serum of patients allergic to Huachansu injection were collected, at the same time, the dubious allergen was conjugated to bovine serum albumin (BSA) by EDC coupling procedure to form complete antigen (BNP-BSA), which makes it possible to reproduce the allergic reaction of Huachansu injection in vitro. The histamine liberation ratio, the level of TNF-alpha and Histamine released from RBL-2H3 mast cell were detected; the above data were compared with those obtained in vivo.
RESULTThe difference of the histamine liberation ratio, the levels of TNF-alpha and histamine of the resibufogenin-BSA group, group of patients allergic to Huachansu injection were not significant compared with those of normal control group. However, there were significant difference in those data among the cinobufagin-BSA group, the blank control and normal control group (P<0.05).
CONCLUSIONThe allergen in the serum collected from patients allergic to Huachansu injection is resibufogenin.
Allergens ; adverse effects ; immunology ; Amphibian Venoms ; adverse effects ; immunology ; Animals ; Anura ; Bufanolides ; adverse effects ; immunology ; Drug Hypersensitivity ; immunology ; Histamine Release ; Humans ; Mast Cells ; immunology ; Medicine, Chinese Traditional
3.Effect of chlorogenic acid on degranulation in mast cell RBL-2H3.
Bo PENG ; Rong HE ; Qihua XU ; Jie GAO ; Yanli LU ; Jianrong LI
China Journal of Chinese Materia Medica 2011;36(7):912-917
OBJECTIVETo provide evidences for evaluating the role of chlorogenic acid (CA) on the adverse reaction of traditional Chinese medicine injection and promoting clinical rational usage of CA, the effect of CA and chlorogenic acid-HSA(CA-HSA) on the degranulation in mast cell RBL-2H3 were compared and the allergenic effect and its mechanism were investigated.
METHODThe unsensitized and sensitized RBL-2H3 cells were used. The releasing rate of histamine and beta-hexosaminidase was detected by colormetric assays. The degranulating rate was detected by neutral red staining and Annexin V positive cell rate was detected by flow cytometry.
RESULTCA and CA-HSA could not induce degranulation in unsensitized RBL-2H3 cells. CA and CA-HSA could significantly increase the release of histamine and beta-hexosaminidase, degranulating rate and Annexin V positive cell rate.
CONCLUSIONCA has strong allergenicity after combination with serum proteins. As an active ingredient of Shuanghuanglian injection, CA is a kind of possible allergen which caused hypersensitivity reactions induced by Shuanghuanglian injection.
Animals ; Cell Degranulation ; drug effects ; Cell Line ; Chlorogenic Acid ; adverse effects ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; adverse effects ; Histamine Release ; drug effects ; Mast Cells ; cytology ; drug effects ; secretion ; Rats ; beta-N-Acetylhexosaminidases ; secretion
4.Inhibitory effects of epigallocatechin gallate on compound 48/80-inducedmast cell activation and passive cutaneous anaphylaxis.
Guang Zhao LI ; Ok Hee CHAI ; Chang Ho SONG
Experimental & Molecular Medicine 2005;37(4):290-296
Epigallocatechin gallate (EGCG) is a principle phenolic antioxidant found in a variety of plants, including green and black tea. The anti-allergic effect of EGCG is unknown. The purpose of this study is to investigate the effects of EGCG on compound 48/80-induced mast cell activation and passive cutaneous anaphylaxis. For this, the influences of EGCG on the compound 48/80-induced cutaneous reaction were measured in vivo and the effects of EGCG on the compound 48/80-induced mast cell activations were examined in vitro. Results are below: as 1) EGCG significantly inhibited compound 48/80-induced passive cutaneous anaphylaxis, 2) the compound 48/80-induced degranulation, calcium influx and histamine release of rat peritoneal mast cells (RPMCs) were significantly inhibited by the pretreatment with EGCG, and 3) the compound 48/80-mediated inhibition of cAMP level in RPMCs was significantly increased by the pretreatment with EGCG. These results suggested that EGCG, the most abundant polyphenol in green tea, inhibits the compound 48/80-induced mast cell activation and the increase of vascular permeability, and potentially serve as effective therapeutic tools for allergic diseases.
Animals
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Antioxidants/*pharmacology
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Catechin/*analogs & derivatives/pharmacology
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Cyclic AMP/metabolism
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Histamine Release/*drug effects
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Mast Cells/*drug effects/metabolism
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Passive Cutaneous Anaphylaxis/*drug effects
;
Rats
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Research Support, Non-U.S. Gov't
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p-Methoxy-N-methylphenethylamine/*antagonists & inhibitors
5.Effect of Qingkailing injection (QKLI) on complement and RBL-2 H3 cells in virto.
Lijing CHEN ; Guoping LIAO ; Yan WANG ; Shuai HE ; Zhongyi ZHANG
China Journal of Chinese Materia Medica 2011;36(14):1884-1888
OBJECTIVETo investigate the effect of Qingkailing injection (QKLI) on complement and RBL-2 H3 cells in virto.
METHODThe mixture of human serums and QKLI were incubated for 30 min in vitro and then the content of SC5 b-9 in the mixture was determined by ELISA. RBL-2 H3 cells were cultured and treated by QKLI. Beta-heosaminidase release rate was measured by coloration method. The content of histamine in supernatant was tested by ELISA.
RESULTThe QKLI can reduce the content of SC5 b-9 (P<0.05) and promote the release of beta-heosaminidase and histamine significantly (P<0.05).
CONCLUSIONQKLI didn't induce the complement activation, but induced the release of beta-heosaminidase and histamine directly. Therefore, the clinical adverse reactions of QKLI in clinic may be pseudoallergy which had no relation with the activation of complement system.
Adolescent ; Adult ; Animals ; Cell Degranulation ; drug effects ; Cell Line, Tumor ; Chemistry, Pharmaceutical ; Complement System Proteins ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; pharmacology ; Hexosaminidases ; secretion ; Histamine Release ; drug effects ; Humans ; Injections ; Rats ; Young Adult
6.Synthesis and anti-histamine release activity of phenyl tetrazole compounds.
Zhi-Yu LI ; Ping-Bo LU ; Hui JI ; Qing SHAO ; Qi-Dong YOU ; Xiao LIU
Acta Pharmaceutica Sinica 2009;44(10):1112-1117
Ongoing effort to find novel antiasthmatic drugs led to the design and synthesis of a series of compounds bearing phenyl tetrazole group based on the SAR study. The important intermediate 3-(1H-tetrazol-5-yl) benzenamine was synthesized from m-nitroaniline via cyclization and hydrogenation. Followed by amidation, eight new target compounds were obtained. The structures of these compounds were confirmed with 1H NMR, ESI-MS and elemental analysis. Their non-specific and specific anti-histamine effects in the mast cell were determined. Compound NP03 could inhibit non-specific histamine release induced by compound 48/80 in mast cell of SD rats.
Animals
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Anti-Asthmatic Agents
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chemical synthesis
;
chemistry
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pharmacology
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Histamine Release
;
drug effects
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Mast Cells
;
drug effects
;
metabolism
;
Molecular Structure
;
Rats
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Rats, Sprague-Dawley
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Structure-Activity Relationship
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Tetrazoles
;
chemical synthesis
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chemistry
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pharmacology
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p-Methoxy-N-methylphenethylamine
;
pharmacology
7.Ovalbumin fused with diphtheria toxin protects mice from ovalbumin induced anaphylactic shock.
Bong Ki LEE ; Young Gun YOO ; Won Young LEE ; Chun Soo HONG ; Jae Ku PARK ; Jai Youl RO
Yonsei Medical Journal 2001;42(1):91-105
For those with allergy, vaccination with a specific allergen has often been used as a major therapeutic measure. However, the universal application of this technique in clinics have been restricted due to its low success rates and the risk of active systemic anaphylactic shock (ASAS). In this regard, we constructed a fusion protein (OVA-DT), ovalbumin (OVA) fused with diphtheria toxin protein (DT), which may exert a specific cytotoxicity to cells bearing OVA-specific IgE. Its therapeutic effect was evaluated in mice (BALB/c) sensitized with OVA (Os-mice). OVA challenges to the OVA-sensitized mice (Os-mice) caused ASAS to death within 30 min, but OVA-DT treatment afforded mice complete protection. When OVA-DT was treated to the Os-mice, none showed the signs of ASAS when re-challenged 48 h after the treatment. OVA-DT itself was not found to be toxic or allergenic in normal mice. The effect of OVA-DT on the biological functions of mast cells was also studied. Binding of OVA-DT to OVA-specific IgE bearing mast cells and the inhibition of histamine release from these cells were observed. In addition, OVA-DT treatment inhibited the proliferation of OVA-specific B cells in mice. In Os-mice treated with OVA-DT, levels of anti-OVA IgG2a in serum and the production of IFN-gamma by splenic lymphocytes were found to increase, but the production of IL-4 by these cells decreased. Re-direction of cytokine profiles from OVA-specific Th2 to OVA-specific Thl is suggested. These results indicate that OVA-DT can protect Os-mice from ASAS due to OVA challenge, because it inactivates OVA-specific IgE-expressing cells, including mast cells and B cells.
Anaphylaxis/prevention | control*
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Animal
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B-Lymphocytes/immunology
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Female
;
Histamine Release/drug effects
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IgE/metabolism
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Interferon Type II/biosynthesis
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Interleukin-4/biosynthesis
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Lymphocyte Transformation/drug effects
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Mast Cells/metabolism
;
Mice
;
Mice, Inbred BALB C
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Ovalbumin/immunology*
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Recombinant Fusion Proteins/therapeutic use*
8.Atrial natriuretic peptide induces rat peritoneal mast cell activation by cGMP-independent and calcium uptake-dependent mechanism.
Ok Hee CHAI ; Young Hoon LEE ; Eui Hyeog HAN ; Hyoung Tae KIM ; Moo Sam LEE ; Chang Ho SONG
Experimental & Molecular Medicine 2000;32(4):179-186
Atrial natriuretic peptide (ANP), a 28 amino acid basic polypeptide, is known to induce histamine release from human and rat mast cells in vitro and cause a wheel formation in rat skin. However, cellular events associated with histamine release are not clearly understood. In this study, we have examined the calcium flux and cGMP formation associated with histamine release in the ANP-treated mast cells. ANP, in vitro, induced mast cell degranulation and histamine release in a dose-dependent manner. ANP also induced an enhanced calcium uptake into cells and increased the cellular level of cGMP in mast cells. A high level of calcium in the media caused an inhibition of ANP-dependent histamine release but enhanced the level of intracellular cGMP of mast cells. ANP inducing a dose-dependent increase in vascular permeability of rat skin was confirmed by the extravasation of the circulating Evans blue. The results indicate ANP induced the histamine release and an increase in vascular permeability through mast cell degranulation in cGMP-independent and calcium uptake-dependent manner.
Animal
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Atrial Natriuretic Factor/*pharmacology
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Biological Transport
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Calcium/*metabolism
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Capillary Permeability
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Cell Degranulation
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Cyclic GMP/*metabolism
;
Dose-Response Relationship, Drug
;
*Histamine Release
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Mast Cells/*drug effects
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Peritoneal Cavity/cytology
;
Rats
9.The effects of cromakalim on the mediator releases from guinea pig lung mast cell activated by specific antigen-antibody reactions.
Jai Youl RO ; Young Nae YIM ; Kyung Hwan KIM
Yonsei Medical Journal 1996;37(5):325-338
The inhibitory effect of cromakalim on the mediator release from mast cells caused by antigenantibody reactions was in controversy with the specific antigen used. However, it has recently been observed that cromakalim inhibits the release of mediators from superfused tracheal and parenchymal strips or lung mast cells after passive sensitization with the IgG1 antibody. An attempt, therefore, was made to determine the inhibitory mechanisms of cromakalim on the release of mediators such as histamine and leukotriene released by the activation of enzymes during mast cell activation. Guinea pig lung mast cells were purified through enzyme digestion, rough percoll and continuous percoll density gradients. The purified mast cells were prelabeled with [3H]palmitic acid. PLD activity was assessed more directly by the production of labeled phosphatidylethanol by PLD-mediated transphosphatidylation in the presence of ethanol. In the cells labelled with [3H]myristic acid, [3H] DAG production was measured. The methyltransferase activity was assessed by measuring the incorporation of [3H]methyl moiety into phospholipids in sensitized mast cells labelled with L-[3H] methylmethionine. cAMP level was measured by radioimmunoassay. Cromakalim resulted in a decrease in the amount of histamine and leukotrienes releases by 30% in the ovalumin-induced mast cell. Cromakalim had little effect on phospholipase D activity enhanced by the activated mast cell. Cromakalim inhibited the initial increase of diacylglycerol production during mast cell activations. Cromakalim inhibited the phospholipid methylation increased in the activated mast cell. These results show that cromakalim decreases histamine release by inhibiting the initial increase of 1,2-diacylglycerol during the mast cell activation, which is mediated via the phosphatidylinositide-phospholipase C system rather than the phosphatidylcholine-phospholipase D system. Furthermore, cromakalim reduces phosphatidylcholine production by inhibiting the methyltransferase, which decreases the conversion of phosphatidylcholine into arachidonic acid and inhibits the production of leukotrienes.
Adenylate Cyclase/metabolism
;
Animal
;
*Antigen-Antibody Reactions
;
Benzopyrans/*pharmacology
;
Cromakalim
;
Diglycerides/biosynthesis
;
Female
;
Guinea Pigs
;
Histamine Release/*drug effects
;
Leukotrienes/*secretion
;
Lung/drug effects/secretion
;
Mast Cells/*drug effects/secretion
;
Methylation
;
Phospholipase D/metabolism
;
Phospholipids/metabolism
;
Potassium Channels/*drug effects
;
Pyrroles/*pharmacology
;
Support, Non-U.S. Gov't
10.The effects of cromakalim on the mediator releases from guinea pig lung mast cell activated by specific antigen-antibody reactions.
Jai Youl RO ; Young Nae YIM ; Kyung Hwan KIM
Yonsei Medical Journal 1996;37(5):325-338
The inhibitory effect of cromakalim on the mediator release from mast cells caused by antigenantibody reactions was in controversy with the specific antigen used. However, it has recently been observed that cromakalim inhibits the release of mediators from superfused tracheal and parenchymal strips or lung mast cells after passive sensitization with the IgG1 antibody. An attempt, therefore, was made to determine the inhibitory mechanisms of cromakalim on the release of mediators such as histamine and leukotriene released by the activation of enzymes during mast cell activation. Guinea pig lung mast cells were purified through enzyme digestion, rough percoll and continuous percoll density gradients. The purified mast cells were prelabeled with [3H]palmitic acid. PLD activity was assessed more directly by the production of labeled phosphatidylethanol by PLD-mediated transphosphatidylation in the presence of ethanol. In the cells labelled with [3H]myristic acid, [3H] DAG production was measured. The methyltransferase activity was assessed by measuring the incorporation of [3H]methyl moiety into phospholipids in sensitized mast cells labelled with L-[3H] methylmethionine. cAMP level was measured by radioimmunoassay. Cromakalim resulted in a decrease in the amount of histamine and leukotrienes releases by 30% in the ovalumin-induced mast cell. Cromakalim had little effect on phospholipase D activity enhanced by the activated mast cell. Cromakalim inhibited the initial increase of diacylglycerol production during mast cell activations. Cromakalim inhibited the phospholipid methylation increased in the activated mast cell. These results show that cromakalim decreases histamine release by inhibiting the initial increase of 1,2-diacylglycerol during the mast cell activation, which is mediated via the phosphatidylinositide-phospholipase C system rather than the phosphatidylcholine-phospholipase D system. Furthermore, cromakalim reduces phosphatidylcholine production by inhibiting the methyltransferase, which decreases the conversion of phosphatidylcholine into arachidonic acid and inhibits the production of leukotrienes.
Adenylate Cyclase/metabolism
;
Animal
;
*Antigen-Antibody Reactions
;
Benzopyrans/*pharmacology
;
Cromakalim
;
Diglycerides/biosynthesis
;
Female
;
Guinea Pigs
;
Histamine Release/*drug effects
;
Leukotrienes/*secretion
;
Lung/drug effects/secretion
;
Mast Cells/*drug effects/secretion
;
Methylation
;
Phospholipase D/metabolism
;
Phospholipids/metabolism
;
Potassium Channels/*drug effects
;
Pyrroles/*pharmacology
;
Support, Non-U.S. Gov't