Dural mast cell degranulation is a putative mechanism for headache induced by PACAP-38

Cephalalgia ◽  
2012 ◽  
Vol 32 (4) ◽  
pp. 337-345 ◽  
Author(s):  
Michael Baun ◽  
Martin Holst Friborg Pedersen ◽  
Jes Olesen ◽  
Inger Jansen-Olesen
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Adenylate Cyclase ◽  
Phospholipase C ◽  
Dura Mater ◽  
Mast Cell Degranulation ◽  
Peritoneal Mast Cell ◽  
Selective Blockade ◽  
Peritoneal Mast Cells

Background: Pituitary adenylate cyclase activating peptide-38 (PACAP-38) has been shown to induce migraine in migraineurs, whereas the related peptide vasoactive intestinal peptide (VIP) does not. In the present study we examine the hypothesis that PACAP-38 and its truncated version PACAP-27 but not VIP cause degranulation of mast cells in peritoneum and in dura mater. Methods: The degranulatory effects of PACAP-38, PACAP-27 and VIP were investigated by measuring the amount of N-acetyl-β-hexosaminidase released from isolated peritoneal mast cells and from dura mater attached to the skull of the rat in vitro. In peritoneal mast cells N-truncated fragments of PACAP-38 (PACAP(6–38), PACAP(16–38) and PACAP(28–38)) were also studied. To investigate transduction pathways involved in mast cell degranulation induced by PACAP-38, PACAP-27 and VIP, the phospholipase C inhibitor U-73122 and the adenylate cyclase inhibitor SQ 22536 were used. Results: The peptides induced degranulation of isolated peritoneal mast cells of the rat with the following order of potency: PACAP-38 = PACAP(6–38) = PACAP(16–38) » PACAP-27 = VIP = PACAP(28–38). In the dura mater we found that 10−5 M PACAP-38 was significantly more potent in inducing mast cell degranulation than the same concentration of PACAP-27 or VIP. Inhibition of intracellular mechanisms demonstrated that PACAP-38-induced degranulation is mediated by the phospholipase C pathway. Selective blockade of the PAC1 receptor did not attenuate degranulation. Conclusion: These findings correlate with clinical studies and support the hypothesis that mast cell degranulation is involved in PACAP-induced migraine. PACAP-38 has a much stronger degranulatory effect on rat peritoneal and dural mast cells than VIP and PACAP-27. The difference in potency between PACAP-38- and PACAP-27/VIP-induced peritoneal mast cell degranulation is probably not related to the PAC1 receptor but is caused by a difference in efficacy on phospholipase C.

scholarly journals Multiple bidirectional alterations of phenotype and changes in proliferative potential during the in vitro and in vivo passage of clonal mast cell populations derived from mouse peritoneal mast cells

Blood ◽  
1988 ◽  
Vol 72 (3) ◽  
pp. 877-885 ◽  
Author(s):  
Y Kanakura ◽  
H Thompson ◽  
T Nakano ◽  
T Yamamura ◽  
H Asai ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Tissue Type ◽  
Cell Populations ◽  
Proliferative Potential ◽  
Heparin Binding ◽  
Peritoneal Mast Cells ◽  
Proliferative Ability

Mouse peritoneal mast cells (PMC) express a connective tissue-type mast cell (CTMC) phenotype, including reactivity with the heparin-binding fluorescent dye berberine sulfate and incorporation of [35S] sulfate predominantly into heparin proteoglycans. When PMC purified to greater than 99% purity were cultured in methylcellulose with IL-3 and IL-4, approximately 25% of the PMC formed colonies, all of which contained both berberine sulfate-positive and berberine sulfate-negative mast cells. When these mast cells were transferred to suspension culture, they generated populations that were 100% berberine sulfate-negative, a characteristic similar to that of mucosal mast cells (MMC), and that synthesized predominantly chondroitin sulfate [35S] proteoglycans. When “MMC-like” cultured mast cells derived from WBB6F1-+/+ PMC were injected into the peritoneal cavities of mast cell-deficient WBB6F1- W/Wv mice, the adoptively transferred mast cell population became 100% berberine sulfate-positive. In methylcellulose culture, these “second generation PMC” formed clonal colonies containing both berberine sulfate-positive and berberine sulfate-negative cells, but exhibited significantly less proliferative ability than did normal +/+ PMC. Thus, clonal mast cell populations initially derived from single PMC exhibited multiple and bidirectional alterations between CTMC-like and MMC-like phenotypes. However, this process was associated with a progressive diminution of the mast cells' proliferative ability.

scholarly journals Glaucocalyxin A Attenuates Allergic Responses by Inhibiting Mast Cell Degranulation through p38MAPK/NrF2/HO-1 and HMGB1/TLR4/NF-κB Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yihua Piao ◽  
Jingzhi Jiang ◽  
Zhiguang Wang ◽  
Chongyang Wang ◽  
Shan Jin ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Calcium Influx ◽  
Mast Cell Degranulation ◽  
Therapeutic Drug ◽  
High Mobility Group Protein

Glaucocalyxin A (GLA) has various pharmacological effects like antioxidation, immune regulation, and antiatherosclerosis. Here, in this study, the effect and mechanism of GLA on mast cell degranulation were studied. The results of the anti-DNP IgE-mediated passive cutaneous anaphylaxis (PCA) showed that GLA dramatically inhibited PCA in vivo, as evidenced by reduced Evans blue extravasation and decreased ear thickness. In addition, GLA significantly reduced the release of histamine and β-hexosaminidase, calcium influx, cytokine (IL-4, TNF-α, IL-1β, IL-13, and IL-8) production in the RBL-2H3 (rat basophilic leukemia cells), and RPMCs (peritoneal mast cells) in vitro. Moreover, we further investigated the regulatory mechanism of GLA on antigen-induced mast cells by Western blot, which showed that GLA inhibited FcεRI-mediated signal transduction and invalidated the phosphorylation of Syk, Fyn, Lyn, Gab2, and PLC-γ1. In addition, GLA inhibited the recombinant mouse high mobility group protein B1- (HMGB1-) induced mast cell degranulation through limiting nuclear translocation of NF-κBp65. Treatment of mast cells with siRNA-HMGB1 significantly inhibited HMGB1 levels, as well as MyD88 and TLR4, decreased intracellular calcium levels, and suppressed the release of β-hexosaminidase. Meanwhile, GLA increased NrF2 and HO-1 levels by activating p38MAPK phosphorylation. Consequently, these data suggest that GLA regulates the NrF2/HO-1 signaling pathway through p38MAPK phosphorylation and inhibits HMGB1/TLR4/NF-κB signaling pathway to reduce mast cell degranulation and allergic inflammation. Our findings could be used as a promising therapeutic drug against allergic inflammatory disease.

scholarly journals Denatonium Benzoate Exposure Promotes IgE-Mediated Mast Cell Degranulation and Allergy By Upregulating FcεRIα Expression

2021 ◽  
Author(s):  
Huaping Xu ◽  
Xiaoyun Shi ◽  
Mengting Xie ◽  
Shiyu Xiao ◽  
Xin Li ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Surface ◽  
Surface Expression ◽  
Specific Ige ◽  
Mast Cell Degranulation ◽  
Cell Surface Expression ◽  
Denatonium Benzoate ◽  
Ige Mediated

Abstract Background: Denatonium benzoate (DB), one of the bitterest compounds known to man, is currently added to a wide range of products and is also used for alcohol denaturation. Some reports demonstrated that asthmatic symptoms are associated with DB exposure but the possible links between DB and IgE-mediated allergy susceptibility have not been examined to date. We investigated the effects of DB on IgE-mediated mast cell degranulation in vitro and in the ovalbumin (OVA)-induced mouse model of allergy.Methods: DB treatments were given to RBL-2H3 IgE-sensitized rat mast cell/basophil cells and KU812 human basophilic cells together with OVA-induced allergic BALB/c mice. Allergic mediator release, Ca2+ influx and OVA-specific IgE anaphylactic shock symptoms were measured along with the cell-surface expression of the α-subunit of high-affinity IgE receptor FcεRI on mast cells.Results: DB increases β-hexosaminidase (β-hex) release and Ca2+ mobilization in IgE-mediated activated RBL-2H3 and KU812 cells, and enhanced the cell-surface expression of FcεRIα. DB also promoted the severity of OVA-induced anaphylactic and diarrheic symptoms which was accompanied by mucus thickness in jejunum and the levels of β-hex, histamine and OVA-specific IgE in allergy mice, as well as the levels of FcεRIα mRNA and the FcεRIα proteinin isolated mucosal mast cells. Conclusions: DB treatments can promote the IgE-mediated mast cell degranulation in vitro and OVA-induced allergic susceptibility in mice by upregulating mast-cell-surface FcεR1α expression, providing evidence for DB exposure in promoting allergy susceptibility.

Mucosal mast cells and developmental changes in gastric absorption

1995 ◽  
Vol 268 (1) ◽  
pp. G121-G127 ◽  
Author(s):  
A. G. Catto-Smith ◽  
J. L. Ripper
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Short Circuit ◽  
Mast Cell Degranulation ◽  
Mucosal Mast Cell ◽  
Sprague Dawley ◽  
Mucosal Permeability ◽  
Mucosal Mast Cells ◽  
Gastric Mucosal Mast Cell

We aimed to establish whether gastric mucosal mast cells undergo degranulation during normal postnatal development and to correlate this with gastric electrical parameters, paracellular permeability, and macromolecular absorption. Sprague-Dawley rats were studied between 10 and 30 days after birth. Gastric mucosal mast cell degranulation occurred and was maximal on days 15 and 17, measured by histology and gastric and serum levels of rat mast cell protease II. Short-circuit current, transepithelial conductance, and permeability of voltage-clamped glandular stomach were elevated in younger animals, falling with age except for a transient but significant increase in conductance and permeability at 17 days, closely correlated with maximal mast cell degranulation. Macromolecular uptake was significantly increased in animals aged 10-15 days. Concanavalin A and antigen-induced mast cell degranulation increased conductance and permeability in vitro in younger animals. We conclude that 1) gastric mucosal mast cells degranulate during development, 2) the neonatal stomach has increased permeability and uptake of macromolecules, and 3) gastric mucosal mast cell degranulation during development may affect mucosal permeability.

Inhibition of Mast Cell-Mediated Anaphylaxis by Sochungryong-Tang

2000 ◽  
Vol 28 (01) ◽  
pp. 69-76 ◽  
Author(s):  
H. M. Kim ◽  
G. S. Yoon ◽  
J. U. Seo ◽  
G. Moon ◽  
H. R. Kim ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Anaphylactic Shock ◽  
Mast Cell Degranulation ◽  
Dependent Manner ◽  
Asian Philosophy ◽  
Peritoneal Mast Cells ◽  
Rat Peritoneal Mast Cells ◽  
Anti Body ◽  
Dose Dependent

According to traditional Asian philosophy, Sochungryong-Tang (S-Tang) is a prescription for treating exterior syndrome. In this study, we investigated the effect of S-Tang on mast cell-mediated anaphylaxis. S-Tang completely inhibited compound 48/80-induced systemic anaphylactic shock at a dose of 100 mg/kg. When S-Tang was given as pretreatment at concentrations ranging from 1 to 1000 mg/kg, the serum histamine levels induced by compound 48/80 were reduced in a dose-dependent manner. S-Tang inhibited the local anaphylaxis activated by anti-dinitrophenyl (DNP) IgE anti-body, and also inhibited the histamine release from the rat peritoneal mast cells by compound 48/80 or anti-DNP IgE. These results indicate that S-Tang may contain substances with actions that inhibit mast cell degranulation.

scholarly journals Effects of Nigella sativa seeds and certain species of fungi extracts on number and activation of dural mast cells in rats

2017 ◽  
Vol 104 (1) ◽  
pp. 15-24 ◽  
Author(s):  
E Kilinc ◽  
Y Dagistan ◽  
B Kotan ◽  
A Cetinkaya
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Dura Mater ◽  
Nigella Sativa ◽  
Tap Water ◽  
Mast Cell Degranulation ◽  
Cell Numbers ◽  
Beneficial Effects ◽  
Tricholoma Terreum ◽  
Mast Cell Degranulating

In this study, we aimed to investigate the effects of Nigella sativa seeds and certain species of fungi extracts on the number and degranulation states of dural mast cells in rats. Rats were fed ad libitum with normal tap water or tap water with extract of N. sativa seed, Ramaria condensata, Lactarius salmonicolor, Lactarius piperatus, and Tricholoma terreum for 3 days. Mast cells in dura mater were counted and evaluated in terms of granulation and degranulation states. Compound 48/80, a mast cell degranulating agent, and T. terreum significantly increased the percent of degranulated mast cells in dura mater, respectively (p < 0.01 and p < 0.05). Moreover, T. terreum causes a significant increase in the total number of mast cells (p < 0.05). N. sativa significantly inhibited mast cell degranulation induced by both the compound 48/80 and T. terreum (p < 0.05), and significantly decreased the mast cell numbers increased by T. terreum (p < 0.05). Our results suggested that T. terreum following ingestion can contribute to headaches like migraine via dural mast cell degranulation and N. sativa may be able to exert analgesic and anti-inflammatory effects by stabilizing dural mast cells. However, investigation is needed to determine the ingredients of N. sativa that may be responsible for these beneficial effects.

TLR3-induced activation of mast cells modulates CD8+ T-cell recruitment

Blood ◽  
2005 ◽  
Vol 106 (3) ◽  
pp. 978-987 ◽  
Author(s):  
Zane Orinska ◽  
Elena Bulanova ◽  
Vadim Budagian ◽  
Martin Metz ◽  
Marcus Maurer ◽  
...  
Keyword(s):  
Mast Cell ◽  
T Cell ◽  
Mast Cells ◽  
Cd8 T Cell ◽  
Poly I:C ◽  
Cell Recruitment ◽  
Polycytidylic Acid ◽  
Peritoneal Mast Cells

AbstractMast cells play an important role in host defense against various pathogens, but their role in viral infection has not been clarified in detail. dsRNA, synthesized by various types of viruses and mimicked by polyinosinic-polycytidylic acid (poly(I:C)) is recognized by Toll-like receptor 3 (TLR3). In this study, we demonstrate that poly(I:C) injection in vivo potently stimulates peritoneal mast cells to up-regulate a number of different costimulatory molecules. Therefore, we examined the expression and the functional significance of TLR3 activation in mast cells. Mast cells express TLR3 on the cell surface and intracellularly. After stimulation of mast cells with poly(I:C) and Newcastle disease virus (NDV), TLR3 is phosphorylated and the expression of key antiviral response cytokines (interferon β, ISG15) and chemokines (IP10, RANTES) is upregulated. Interestingly, mast cells activated via TLR3-poly(I:C) potently stimulate CD8+ T-cell recruitment. Indeed, mast-cell–deficient mice (KitW/KitW-v) given an intraperitoneal injection of poly(I:C) show a decreased CD8+ T-cell recruitment, whereas granulocytes normally migrate to the peritoneal cavity. Mast-cell reconstitution of KitW/KitW-v mice normalizes the CD8+ T-cell influx. Thus, mast cells stimulated through engagement of TLR3 are potent regulators of CD8+ T-cell activities in vitro and in vivo.

Modulatory action of potassium channel openers on field potential and histamine release from rat peritoneal mast cells

2009 ◽  
Vol 87 (8) ◽  
pp. 624-632 ◽  
Author(s):  
Chi-Kong Yeung ◽  
Jessica Ka-Yan Law ◽  
Sze-Wing Sam ◽  
Sven Ingebrandt ◽  
Hang-Yung Alaster Lau ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Potassium Channel ◽  
Histamine Release ◽  
Field Potential ◽  
Peritoneal Mast Cell ◽  
Induced Response ◽  
Potassium Channel Openers ◽  
Peritoneal Mast Cells ◽  
Rat Peritoneal Mast Cells

To determine whether changes in membrane potential affect the extent of mast cell degranulation, compound 48/80 was added to rat peritoneal mast cell suspensions in the absence or presence of potassium channel openers (KCOs). Changes were compared between the field potential (FP) and the amount of histamine released. The results demonstrated that (i) the onset and duration of FP, which reflects the hyperpolarizing nature of the response, increased as the concentration of compound 48/80 increased; (ii) both FP and the amount of histamine released increased as the concentration of compound 48/80 increased; (iii) although both KCOs (SDZ PCO400, a benzopyran derivative, and P1060, a cyanoguanidine derivative) potentiated compound 48/80-induced increases in FP and histamine release, without compound 48/80, they had no effect on either parameter; (iv) both glibenclamide and charybdotoxin significantly attenuated the compound 48/80-induced increase in FP; and (v) glibenclamide was able to attenuate the KCO-induced potentiation of FP. The results show that drugs presumably causing hyperpolarization can affect histamine release from rat peritoneal mast cells. The effect of KCOs on compound 48/80-induced response appears to be potentiation in nature rather than synergism. It is possible that KCO hyperpolarizes the cell membrane, enhances Ca2+ influx, and thus increases histamine release. As such, selective blockers of K+ channels may be useful for the treatment of immunological disorders.

Clinacanthus nutans Aqueous Extract But Not Ethanolic Extract Inhibits the Release of Preformed Mediators in In Vitro Model of IgE-Mediated Mast Cell Degranulation

2017 ◽  
Vol 1 (2) ◽  
Author(s):  
Audrey Siew Foong Kow ◽  
Lai Yen Fong ◽  
Leng Wei Khoo ◽  
Ji Wei Tan ◽  
Khozirah Shaari ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Aqueous Extract ◽  
Inflammatory Mediators ◽  
Scientific Evidence ◽  
Ethanolic Extract ◽  
Mast Cell Degranulation ◽  
Traditional Use ◽  
Medicinal Uses

C. nutans (Burm. f.) Lindau is a shrub that is commonly found in South East Asia, particularly in Malaysia, Thailand and Indonesia. This plant has diverse and potential medicinal uses in traditional herbal medicine for treating many diseases which include skin rashes. Skin rash is one of the symptoms that primarily occur in people with allergies. Till date, there has been no scientific evidence to support this traditional use of C. nutans as well as its potential of possessing anti-allergic properties. IgE and mast cells play an important role in the pathogenesis of allergy. Upon cross-linking of allergen to IgE antibodies bound to FcεRI on mast cells, pro-inflammatory mediators will be released as a result of degranulation. The release of pro-inflammatory mediators by mast cells activated by allergen in the skin causes large, itchy, red swellings of the skin. This study aimed to identify the most active C. nutans extract in inhibiting in vitro IgE-mast cell degranulation. Rat basophilic leukaemic cells (RBL-2H3) were pre-sensitised with IgE, pre-treated with C. nutans ethanolic (100%, 70% and 50%) or aqueous extracts and challenged with dinitrophenyl-bovine serum albumin (DNP-BSA) accordingly to analyse the release of β-hexosaminidase, histamine, interleukin (IL)-4 and tumour necrosis factor (TNF)-α. It was found that C. nutans aqueous extract was the most active extract compared to the ethanolic extracts as it was able to inhibit the release of β-hexosaminidase and histamine at concentrations of 5 mg/ml and above.

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