NE inhibits cerebrovascular mast cell exocytosis induced by cholinergic and peptidergic agonists

1997 ◽  
Vol 273 (3) ◽  
pp. R845-R850
Author(s):  
A. M. Reynier-Rebuffel ◽  
J. Callebert ◽  
J. M. Launay ◽  
J. Seylaz ◽  
P. Aubineau
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Ex Vivo ◽  
Inhibitory Effect ◽  
Sensory Nerves ◽  
Mast Cell Granule ◽  
Adrenergic Blocker ◽  
Adrenergic Blockers ◽  
Beta 2 ◽  
Dose Dependent

Autonomic and sensory nerves frequently contact mast cells contained in rabbit leptomeningeal arteries. We have previously shown that parasympathetic and peptidergic neurotransmitters can stimulate mast cell granule exocytosis and serotonin (5-HT) release. In the present study, we examined ex vivo the possible action of the main sympathetic neurotransmitter, norepinephrine (NE), on this exocytotic process. NE, which had no effect on mast cell 5-HT content per se, totally inhibited carbachol-induced 5-HT release and partially reduced neuropeptide-induced 5-HT release. Pretreatment with the alpha 1-adrenergic blocker did not affect the inhibitory effect of NE. Pretreatment with specific beta 1- or beta 2-adrenergic blockers antagonized this action, but the beta 2-blocker exerts a more specific dose-dependent antagonism. Together with our previous data, these results indicate that the equilibrium between autonomic and sensory nerves may determine the release of 5-HT from mast cells (parasympathetic and sensory nerves can trigger exocytosis while the sympathetics can inhibit it). Such a mechanism could be implicated in pathophysiological events in which autonomic dysfunction is likely to be involved, such as vascular headache or other phenomena involving inflammation.

Cytochemical analysis of mast cell granules after poly-dl-lysine action

1978 ◽  
Vol 36 (2) ◽  
pp. 278-279
Author(s):  
R. Courtoy ◽  
L.J. Simar ◽  
J. Christophe
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Chemical Compounds ◽  
Cellular Membrane ◽  
Thin Sections ◽  
Organic Bases ◽  
Ferric Thiocyanate ◽  
Cytochemical Analysis ◽  
Mast Cell Granule ◽  
Amine Liberation

Several chemical compounds induce amine liberation from mast cells but do not necessarily provoque the granule expulsion. For example, poly-dl-lysine induces modifications of the cellular membrane permeability which promotes ion exchange at the level of mast cell granules. Few of them are expulsed but the majority remains in the cytoplasm and appears less dense to the electrons. A cytochemical analysis has been performed to determine the composition of these granules after the polylysine action.We have previously reported that it was possible to demonstrate polyanions on epon thin sections using a cetylpyridinium ferric thiocyanate method. Organic bases are selectively stained with cobalt thiocyanate and the sulfhydryle groups are characterized with a silver methenamine reaction. These techniques permit to reveal the mast cell granule constituents, i.e. heparin, biogenic amines and basic proteins.

Mast cell-nerve fiber interaction: Ultrastructural studies

1990 ◽  
Vol 48 (3) ◽  
pp. 428-429
Author(s):  
E.Y. Chi ◽  
M.L. Su ◽  
Y.T. Tien ◽  
W.R. Henderson
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Substance P ◽  
Nerve Fiber ◽  
Sensory Nerves ◽  
Ultrastructural Studies ◽  
Morphological Studies ◽  
Granulocyte Infiltration ◽  
Intracutaneous Injection ◽  
Recent Attention

Recent attention has been directed to the interaction of the nerve and immune systems. The neuropeptide substance P, a tachykinnin which is a neurotransmitter in the central and peripheral nervous systems produces tissue swelling, augemntation of intersitial fibrin deposition and leukocyte infiltration after intracutaneous injection. There is a direct correlation reported between the extent of mast cell degranulation at the sites of injection and the tissue swelling or granulocyte infiltration. It has previously been demonstrated that antidromic electrical stimulation of sensory nerves induces degranulation of cutaneous mast cells, cutaneous vasodilation and augmented vascular permeability. Morphological studies have documented a close anatiomical association between mast cells and nonmyelinated nerves, that contain substance P and other neuropeptides. However, the presence of mast cells within nerve fasicles has not been previously examined ultrastructurally. In this study, we examined ultrastructurally the distribution of mast cells in the nerve fiber bundles located in the muscular connective tissue of rat tongues (n=20).

Abstract 1193: Mast Cell Activation Promotes Leukocyte Recruitment And Adhesion To The Atherosclerotic Plaque

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Ilze Bot ◽  
Saskia C de Jager ◽  
Alma Zernecke ◽  
Christian Weber ◽  
Theo J van Berkel ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Carotid Artery ◽  
Atherosclerotic Plaque ◽  
Cell Activation ◽  
Ex Vivo ◽  
Leukocyte Adhesion ◽  
Leukocyte Recruitment ◽  
Mast Cell Activation ◽  
Labeled Leukocytes

Activated mast cells have been identified in the perivascular tissue of human coronary artery plaques. As mast cells have been described to release a whole array of chemokines including interleukin 8 (IL-8) and MIP1 α, we propose that activated mast cells play a pivotal role in leukocyte recruitment at advanced stages of atherosclerotic plaque development. Peritoneal mast cells of either C57Bl/6 or mast cell deficient Kit(W −sh /W −sh ) mice were activated by injection of compound 48/80 (1.2 mg/kg). Interestingly, mast cell activation led to a massive neutrophil influx into the peritoneal cavity at 3 hours after activation (controls: 1 ± 0.7*10 4 Gr1 + -neutrophils/ml up to 8 ± 0.2*10 4 Gr1 + neutrophils/ml at 3 hours after activation, *P<0.05), while neutrophil numbers in Kit(W −sh /W −sh ) mice were not affected by compound 48/80 administration. Moreover, increased levels of CXCR2 + Gr1 + neutrophils (t=0: 0.55 ± 0.07% versus t=3 hours: 1.00 ± 0.12%, *P<0.05) were observed after mast cell activation. Next, we investigated whether mast cell activation also translated in induced leukocyte adhesion to advanced atherosclerotic plaques. Adventitial mast cells of advanced collar aided carotid artery plaques were activated by local application of a dinitrophenyl-BSA (DNP) challenge in ApoE −/− mice. Three days later, the carotid artery segments carrying the plaques were isolated and perfused ex vivo with rhodamine labeled leukocytes, showing a dramatically increased number of adherent leukocytes after mast cell activation (49 ± 6 versus 19 ± 4 leukocytes/microscopic field for DNP versus control plaques, respectively, **P<0.001). Strikingly, antibody blockade of either the CXCR2 or VCAM-1 receptor VLA-4 on labeled leukocytes completely inhibited leukocyte adhesion to the atherosclerotic plaque (*P<0.05), while blockade of CCR1, -3 and -5 with Met-RANTES had no effect. In conclusion, our data suggest that chemokines such as IL-8 released from activated perivascular mast cells induce leukocyte recruitment and adhesion to the atherosclerotic plaque, aggravating the ongoing inflammatory response and thus effecting plaque destabilization. We propose that mast cell stabilization could be a new therapeutic approach in the prevention of acute coronary syndromes.

Mast cells are involved in the gastric hyperemic response to acid back diffusion via release of histamine

2001 ◽  
Vol 280 (6) ◽  
pp. G1061-G1069 ◽  
Author(s):  
Astrid Rydning ◽  
Oddveig Lyng ◽  
Birgitte Lid Adamsen ◽  
Sture Falkmer ◽  
Arne K. Sandvik ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Chromogranin A ◽  
Ex Vivo ◽  
Back Diffusion ◽  
Rat Stomach ◽  
Stomach Mucosa ◽  
Mucosal Mast Cells ◽  
Receptor Blockers ◽  
Hyperemic Response

Acid back diffusion into the rat stomach mucosa leads to gastric vasodilation. We hypothesized that histamine, if released from the rat mucosa under such conditions, is mast cell derived and involved in the vasodilator response. Gastric blood flow (GBF) and luminal histamine were measured in an ex vivo chamber. Venous histamine was measured from totally isolated stomachs. Mucosal mast cells (MMC), submucosal connective tissue mast cells (CTMC), and chromogranin A-immunoreactive cells (CgA IR) were assessed morphometrically. After mucosal exposure to 1.5 M NaCl, the mucosa was subjected to saline at pH 5.5 (control) or pH 1.0 (H+back diffusion) for 60 min. H+back diffusion evoked a marked gastric hyperemia, increase of luminal and venous histamine, and decreased numbers of MMC and CTMC. CgA IR cells were not influenced. Depletion of mast cells with dexamethasone abolished (and stabilization of mast cells with ketotifen attenuated) both hyperemia and histamine release in response to H+back diffusion. GBF responses to H+back diffusion were attenuated by H1and abolished by H3but not H2receptor blockers. Our data conform to the idea that mast cells are involved in the gastric hyperemic response to acid back diffusion via release of histamine.

Inhibitory Effect of Retinoic Acid on Proliferation, Maturation and Tryptase Level in Human Leukemic Mast Cells (HMC-1)

2003 ◽  
Vol 16 (1) ◽  
pp. 43-47 ◽  
Author(s):  
M.G. Alexandrakis ◽  
D.S. Kyriakou ◽  
D. Seretakis ◽  
W. Boucher ◽  
R. Letourneau ◽  
...  
Keyword(s):  
Mast Cell ◽  
Retinoic Acid ◽  
Mast Cells ◽  
Allergic Inflammation ◽  
Inhibitory Effect ◽  
Control Group ◽  
Tryptase Level ◽  
Synthetic Derivatives ◽  
Derivatives Of ◽  
Inhibit Cell Proliferation

Mast cells play an important role in allergic inflammation by releasing histamine, tryptase and several inflammatory cytokines. Human leukemic mast cells (HMC-1) have been used to study mast cell mediators and their role in inflammatory mechanisms. HMC-1 contain and release several inflammatory mediators, of which the proteolytic enzyme tryptase is most characteristic. Retinoids, including retinoic acid, are naturally occurring and synthetic derivatives of vitamin A. All-trans-retinoic (ATRA) acid had been previously reported to inhibit cell proliferation, differentiation and apoptosis. In the present study, we investigated the effect of ATRA on the proliferation and secretion of tryptase in HMC-1. HMC-1 were treated with ATRA at 10-4M, 10-5M or 10-6M for 3,4 or 5 days in culture. Control HMC-1 were treated with equal amount of culture medium only. ATRA decreased the number of HMC-1 as compared to the control group. The same treatment for 3, 4 or 5 days also decreased intracellular tryptase levels. These results indicate that ATRA significantly inhibits both proliferation and growth as shown by the decreased intracellular tryptase levels in HMC-1. ATRA may be a useful agent in the treatment of mast cell proliferative disorders.

scholarly journals AR-42, a novel HDAC inhibitor, exhibits biologic activity against malignant mast cell lines via down-regulation of constitutively activated Kit

Blood ◽  
2010 ◽  
Vol 115 (21) ◽  
pp. 4217-4225 ◽  
Author(s):  
Tzu-Yin Lin ◽  
Joelle Fenger ◽  
Sridhar Murahari ◽  
Misty D. Bear ◽  
Samuel K. Kulp ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Lines ◽  
Histone Deacetylase Inhibitors ◽  
Ex Vivo ◽  
Histone Deacetylation ◽  
Down Regulation ◽  
Biologic Activity ◽  
Promising Therapeutic Approach

Histone hypoacetylation occurs in many cancers and inhibition of histone deacetylation is a promising approach to modulate these epigenetic changes. Our laboratory previously demonstrated that the histone deacetylase inhibitors (HDACis) vorinostat and AR-42 reduced the viability of a canine malignant mast cell line. The purpose of this study was to further investigate the mechanisms of pan-HDAC inhibition in normal and malignant mast cells. Mouse and canine malignant mast cell lines expressing various Kit mutations, normal canine mast cells, and primary canine malignant mast cells were treated with AR-42 (a novel HDACi) and effects on cell viability, cycling, and signaling were evaluated. Treatment with AR-42 induced growth inhibition, cell- cycle arrest, apoptosis, and activation of caspases-3/7. AR-42 promoted hyperacetylation of H3, H4, and alpha-tubulin, and up-regulation of p21. Down-regulation of Kit occurred after AR-42 treatment via inhibition of Kit transcription. Disassociation between Kit and heat shock protein 90 (HSP90) and up-regulation of HSP70 were observed after AR-42 treatment, suggesting potential loss of HSP90 chaperone function. Lastly, AR-42 down-regulated the expression of p-Akt, total Akt, phosphorylated STAT3/5 (pSTAT3/5), and total STAT3/5. In summary, AR-42 exhibits in vitro and ex vivo biologic activity against malignant mast cells, representing a promising therapeutic approach for malignant mast cell disease.

scholarly journals Neuro-immune interactions in chemical-induced airway hyperreactivity

2016 ◽  
Vol 48 (2) ◽  
pp. 380-392 ◽  
Author(s):  
Fien C. Devos ◽  
Brett Boonen ◽  
Yeranddy A. Alpizar ◽  
Tania Maes ◽  
Valérie Hox ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Transient Receptor Potential ◽  
Chinese Hamster ◽  
Transient Receptor Potential Channels ◽  
Airway Hyperreactivity ◽  
Sensory Nerves ◽  
Wild Type ◽  
Immunological Parameters

Asthma may be induced by chemical sensitisers,viamechanisms that are still poorly understood. This type of asthma is characterised by airway hyperreactivity (AHR) and little airway inflammation. Since potent chemical sensitisers, such as toluene-2,4-diisocyanate (TDI), are also sensory irritants, it is suggested that chemical-induced asthma relies on neuro-immune mechanisms.We investigated the involvement of transient receptor potential channels (TRP) A1 and V1, major chemosensors in the airways, and mast cells, known for their ability to communicate with sensory nerves, in chemical-induced AHR.In vitrointracellular calcium imaging and patch-clamp recordings in TRPA1- and TRPV1-expressing Chinese hamster ovarian cells showed that TDI activates murine TRPA1, but not TRPV1. Using anin vivomodel, in which an airway challenge with TDI induces AHR in TDI-sensitised C57Bl/6 mice, we demonstrated that AHR does not develop, despite successful sensitisation, inTrpa1andTrpv1knockout mice, and wild-type mice pretreated with a TRPA1 blocker or a substance P receptor antagonist. TDI-induced AHR was also abolished in mast cell deficientKitWsh/Wshmice, and in wild-type mice pretreated with the mast cell stabiliser ketotifen, without changes in immunological parameters.These data demonstrate that TRPA1, TRPV1 and mast cells play an indispensable role in the development of TDI-elicited AHR.

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