scholarly journals Stress-Induced Mast Cell Activation in Glabrous and Hairy Skin

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Constantin Căruntu ◽  
Daniel Boda ◽  
Sorin Musat ◽  
Ana Căruntu ◽  
Eugen Mandache
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Prolonged Exposure ◽  
Mast Cell Degranulation ◽  
Mast Cell Activation ◽  
Glabrous Skin ◽  
Stress Exposure ◽  
Hairy Skin ◽  
The Impact

Mast cells play a key role in modulation of stress-induced cutaneous inflammation. In this study we investigate the impact of repeated exposure to stress on mast cell degranulation, in both hairy and glabrous skin. Adult male Wistar rats were randomly divided into four groups: Stress 1 day(n=8), Stress 10 days(n=7), Stress 21 days(n=6), and Control(n=8). Rats in the stress groups were subjected to 2 h/day restraint stress. Subsequently, glabrous and hairy skin samples from animals of all groups were collected to assess mast cell degranulation by histochemistry and transmission electron microscopy. The impact of stress on mast cell degranulation was different depending on the type of skin and duration of stress exposure. Short-term stress exposure induced an amplification of mast cell degranulation in hairy skin that was maintained after prolonged exposure to stress. In glabrous skin, even though acute stress exposure had a profound stimulating effect on mast cell degranulation, it diminished progressively with long-term exposure to stress. The results of our study reinforce the view that mast cells are active players in modulating skin responses to stress and contribute to further understanding of pathophysiological mechanisms involved in stress-induced initiation or exacerbation of cutaneous inflammatory processes.

scholarly journals Mast cell activation is not required for induction of airway hyperresponsiveness by ozone in mice

1999 ◽  
Vol 86 (1) ◽  
pp. 202-210 ◽  
Author(s):  
N. Noviski ◽  
J. P. Brewer ◽  
W. A. Skornik ◽  
S. J. Galli ◽  
J. M. Drazen ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Airway Hyperresponsiveness ◽  
Essential Role ◽  
Cell Activation ◽  
Mast Cell Degranulation ◽  
Mast Cell Activation ◽  
Polymorphonuclear Cell ◽  
Pulmonary Parenchyma

Exposure to ambient ozone (O3) is associated with increased exacerbations of asthma. We sought to determine whether mast cell degranulation is induced by in vivo exposure to O3in mice and whether mast cells play an essential role in the development of pulmonary pathophysiological alterations induced by O3. For this we exposed mast cell-deficient WBB6F1- kitW/ kitW-v( kitW/ kitW-v) mice and the congenic normal WBB6F1(+/+) mice to air or to 1 or 3 parts/million O3for 4 h and studied them at different intervals from 4 to 72 h later. We found evidence of O3-induced cutaneous, as well as bronchial, mast cell degranulation. Polymorphonuclear cell influx into the pulmonary parenchyma was observed after exposure to 1 part/milllion O3only in mice that possessed mast cells. Airway hyperresponsiveness to intravenous methacholine measured in vivo under pentobarbital anesthesia was observed in both kitW/ kitW-vand +/+ mice after exposure to O3. Thus, although mast cells are activated in vivo by O3and participate in O3-induced polymorphonuclear cell infiltration into the pulmonary parenchyma, they do not participate detectably in the development of O3-induced airway hyperresponsiveness in mice.

scholarly journals Regulation of mast cell survival and function by tuberous sclerosis complex 1

Blood ◽  
2012 ◽  
Vol 119 (14) ◽  
pp. 3306-3314 ◽  
Author(s):  
Jinwook Shin ◽  
Hongjie Pan ◽  
Xiao-Ping Zhong
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Survival ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Cell Activation ◽  
Cytokine Production ◽  
Mast Cell Degranulation ◽  
Mtor Signaling ◽  
Mast Cell Activation

Abstract Mast cells play critical roles in allergic disorders and asthma. The importance of tuberous sclerosis complex 1/2-mammalian target of rapamycin (TSC1/2-mTOR) signaling in mast cells is unknown. Here, we report that TSC1 is a critical regulator for mTOR signaling in mast cells downstream of FcεRI and c-Kit, and differentially controls mast cell degranulation and cytokine production. TSC1-deficiency results in impaired mast cell degranulation, but enhanced cytokine production in vitro and in vivo after FcεRI engagement. Furthermore, TSC1 is critical for mast cell survival through multiple pathways of apoptosis including the down-regulation of p53, miR-34a, reactive oxygen species, and the up-regulation of Bcl-2. Together, these findings reveal that TSC1 is a critical regulator of mast cell activation and survival, suggesting the manipulation of the TSC1/2-mTOR pathway as a therapeutic strategy for mast cell-mediated diseases.

Mast cells mediate the microvascular inflammatory response to systemic hypoxia

2003 ◽  
Vol 94 (1) ◽  
pp. 325-334 ◽  
Author(s):  
Dawn R. S. Steiner ◽  
Norberto C. Gonzalez ◽  
John G. Wood
Keyword(s):  
Nitric Oxide ◽  
Mast Cell ◽  
Mast Cells ◽  
Inflammatory Response ◽  
Vascular Permeability ◽  
Cell Activation ◽  
Mast Cell Degranulation ◽  
Mast Cell Activation ◽  
Leukocyte Adherence ◽  
Systemic Hypoxia

Systemic hypoxia produces an inflammatory response characterized by increases in reactive O2 species (ROS), venular leukocyte-endothelial adherence and emigration, and vascular permeability. Inflammation is typically initiated by mediators released from activated perivascular cells that generate the chemotactic gradient responsible for extravascular leukocyte accumulation. These experiments were directed to study the possible participation of mast cells in hypoxia-induced microvascular inflammation. Mast cell degranulation, ROS levels, leukocyte adherence and emigration, and vascular permeability were studied in the mesenteric microcirculation by using intravital microscopy of anesthetized rats. The main findings were 1) activation of mast cells with compound 48/80 in normoxia produced microvascular effects similar, but not identical, to those of hypoxia; 2) systemic hypoxia resulted in rapid mast cell degranulation; 3) blockade of mast cell degranulation with cromolyn prevented or attenuated the hypoxia-induced increases in ROS, leukocyte adherence/emigration, and vascular permeability; and 4) mast cell degranulation during hypoxia was prevented by administration of the antioxidant lipoic acid and of nitric oxide. These results show that mast cells play a key role in hypoxia-induced inflammation and suggest that alterations in the ROS-nitric oxide balance may be involved in mast cell activation during hypoxia.

scholarly journals Identification of 5-Hydroxymethylfurfural (5-HMF) as an Active Component Citrus Jabara That Suppresses FcεRI-Mediated Mast Cell Activation

2020 ◽  
Vol 21 (7) ◽  
pp. 2472 ◽  
Author(s):  
Ryota Uchida ◽  
Michiko Kato ◽  
Yuka Hattori ◽  
Hiroko Kikuchi ◽  
Emi Watanabe ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Active Component ◽  
Cell Activation ◽  
Cytokine Production ◽  
Citrus Fruit ◽  
Mast Cell Degranulation ◽  
Mast Cell Activation ◽  
Active Components ◽  
Seasonal Allergies

Jabara (Citrus jabara Hort. ex Y. Tanaka) is a type of citrus fruit known for its beneficial effect against seasonal allergies. Jabara is rich in the antioxidant narirutin whose anti-allergy effect has been demonstrated. One of the disadvantages in consuming Jabara is its bitter flavor. Therefore, we fermented the fruit to reduce the bitterness and make Jabara easy to consume. Here, we examined whether fermentation alters the anti-allergic property of Jabara. Suppression of degranulation and cytokine production was observed in mast cells treated with fermented Jabara and the effect was dependent on the length of fermentation. We also showed that 5-hydroxymethylfurfural (5-HMF) increases as fermentation progresses and was identified as an active component of fermented Jabara, which inhibited mast cell degranulation. Mast cells treated with 5-HMF also exhibited reduced degranulation and cytokine production. In addition, we showed that the expression levels of phospho-PLCγ1 and phospho-ERK1/2 were markedly reduced upon FcεRI stimulation. These results indicate that 5-HMF is one of the active components of fermented Jabara that is involved in the inhibition of mast cell activation.

scholarly journals New Regulatory Roles of Galectin-3 in High-Affinity IgE Receptor Signaling

2016 ◽  
Vol 36 (9) ◽  
pp. 1366-1382 ◽  
Author(s):  
Monika Bambouskova ◽  
Iva Polakovicova ◽  
Ivana Halova ◽  
Gautam Goel ◽  
Lubica Draberova ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Mast Cell Degranulation ◽  
Negative Regulator ◽  
Mast Cell Activation ◽  
High Affinity ◽  
Galectin 3 ◽  
High Affinity Receptor ◽  
High Affinity Ige Receptor

Aggregation of the high-affinity receptor for IgE (FcεRI) in mast cells initiates activation events that lead to degranulation and release of inflammatory mediators. To better understand the signaling pathways and genes involved in mast cell activation, we developed a high-throughput mast cell degranulation assay suitable for RNA interference experiments using lentivirus-based short hairpin RNA (shRNA) delivery. We tested 432 shRNAs specific for 144 selected genes for effects on FcεRI-mediated mast cell degranulation and identified 15 potential regulators. In further studies, we focused on galectin-3 (Gal3), identified in this study as a negative regulator of mast cell degranulation. FcεRI-activated cells with Gal3 knockdown exhibited upregulated tyrosine phosphorylation of spleen tyrosine kinase and several other signal transduction molecules and enhanced calcium response. We show that Gal3 promotes internalization of IgE-FcεRI complexes; this may be related to our finding that Gal3 is a positive regulator of FcεRI ubiquitination. Furthermore, we found that Gal3 facilitates mast cell adhesion and motility on fibronectin but negatively regulates antigen-induced chemotaxis. The combined data indicate that Gal3 is involved in both positive and negative regulation of FcεRI-mediated signaling events in mast cells.

Human mast cells release the migraine-inducing factor pituitary adenylate cyclase-activating polypeptide (PACAP)

Cephalalgia ◽  
2017 ◽  
Vol 38 (9) ◽  
pp. 1564-1574 ◽  
Author(s):  
Angela J Okragly ◽  
S Michelle Morin ◽  
David DeRosa ◽  
Andrea P Martin ◽  
Kirk W Johnson ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Adenylate Cyclase ◽  
Cell Activation ◽  
Mast Cell Degranulation ◽  
Biologically Active ◽  
Mast Cell Activation ◽  
Human Mast Cells ◽  
Pituitary Adenylate Cyclase ◽  
Ige Mediated

Background Many patients with migraines suffer from allergies and vice versa, suggesting a relationship between biological mechanisms of allergy and migraine. It was proposed many years ago that mast cells may be involved in the pathophysiology of migraines. We set out to investigate the relationship between mast cell activation and known neurogenic peptides related to migraine. Methods Cultured human mast cells were assayed for the presence of neuropeptides and their receptors at the RNA and protein level. Immunohistochemistry analyses were performed on tissue resident and cultured mast cells. Mast cell degranulation assays were performed and pituitary adenylate cyclase-activating polypeptide (PACAP) activity was measured with a bioassay. Results We found that cultured and tissue resident human mast cells contain PACAP in cytoplasmic granules. No other neurogenic peptide known to be involved in migraine was detected, nor did mast cells express the receptors for PACAP or other neurogenic peptides. Furthermore, mast cell degranulation through classic IgE-mediated allergic mechanisms led to the release of PACAP. The PACAP released from mast cells was biologically active, as demonstrated using PACAP receptor reporter cell lines. We confirmed existing literature that mast cell degranulation can also be induced by several neurogenic peptides, which also resulted in PACAP release. Conclusion Our data provides a potential biological explanation for the association between allergy and migraine by demonstrating the release of biologically active PACAP from mast cells.

scholarly journals Differences in the behavior of cytoplasmic granules and lipid bodies during human lung mast cell degranulation.

1984 ◽  
Vol 99 (5) ◽  
pp. 1678-1687 ◽  
Author(s):  
A M Dvorak ◽  
I Hammel ◽  
E S Schulman ◽  
S P Peters ◽  
D W MacGlashan ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Human Lung ◽  
Specific Antigen ◽  
Mast Cell Degranulation ◽  
Mast Cell Activation ◽  
Lipid Bodies ◽  
Cytoplasmic Granules ◽  
Lung Mast Cell

We used a morphometric and autoradiographic approach to analyze changes in specific cytoplasmic granules and cytoplasmic lipid bodies associated with human lung mast cell degranulation. Mast cells were dissociated from lung tissue by enzymatic digestion and were then enriched to purities of up to 99% by countercurrent centrifugation elutriation and recovery from columns containing specific antigen bound to Sepharose 6 MB. Degranulation was induced by goat anti-IgE. At various intervals after stimulation, parallel aliquots of cells were recovered for determination of histamine release or were fixed for transmission electron microscopy. We found that lipid bodies, electron-dense structures that lack unit membranes, were present in both control and stimulated mast cells. Autoradiographic analysis showed that lipid bodies represented the major repository of 3H-label derived from [3H]arachidonic acid taken up from the external milieu. By contrast, the specific cytoplasmic granules contained no detectable 3H-label. In addition, lipid bodies occurred in intimate association with degranulation channels during mast cell activation, but the total volume of lipid bodies did not change during the 20 min after stimulation with anti-IgE. This result stands in striking contrast to the behavior of specific cytoplasmic granules, the great majority of which (77% according to aggregate volume) exhibited ultrastructural alterations during the first 20 min of mast cell activation. These observations establish that mast cell cytoplasmic granules and cytoplasmic lipid bodies are distinct organelles that differ in ultrastructure, biochemistry, and behavior during mast cell activation.

scholarly journals Brain mast cells link the immune system to anxiety-like behavior

2008 ◽  
Vol 105 (46) ◽  
pp. 18053-18057 ◽  
Author(s):  
Katherine M. Nautiyal ◽  
Ana C. Ribeiro ◽  
Donald W. Pfaff ◽  
Rae Silver
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Neural Systems ◽  
Loss Of Function ◽  
Littermate Control ◽  
Cytokines And Chemokines ◽  
Function Models ◽  
The Brain

Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient KitW−sh/W−sh (sash−/−) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links.

Association of Mast Cell Burden and TIM-3 Expression with Recalcitrant Chronic Rhinosinusitis with Nasal Polyps

2021 ◽  
pp. 000348942199503
Author(s):  
Michael A. Belsky ◽  
Erica Corredera ◽  
Hridesh Banerjee ◽  
John Moore ◽  
Li Wang ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Cell Activation ◽  
Enzymatic Digestion ◽  
Sinus Surgery ◽  
Mast Cell Activation ◽  
Need For Treatment ◽  
Inflammatory State

Objectives: Previous work showed that higher polyp mast cell load correlated with worse postoperative endoscopic appearance in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Polyp epithelial mast cells showed increased expression of T-cell/transmembrane immunoglobulin and mucin domain protein 3 (TIM-3), a receptor that promotes mast cell activation and cytokine production. In this study, CRSwNP patients were followed post-operatively to investigate whether mast cell burden or TIM-3 expression among mast cells can predict recalcitrant disease. Methods: Nasal polyp specimens were obtained via functional endoscopic sinus surgery (FESS) and separated into epithelial and stromal layers via enzymatic digestion. Mast cells and TIM-3-expressing mast cells were identified via flow cytometry. Mann-Whitney U tests and Cox proportional hazard models assessed whether mast cell burden and TIM-3 expression were associated with clinical outcomes, including earlier recurrence of polypoid edema and need for treatment with steroids. Results: Twenty-three patients with CRSwNP were studied and followed for 6 months after undergoing FESS. Higher mast cell levels were associated with earlier recurrence of polypoid edema: epithelial HR = 1.283 ( P = .02), stromal HR = 1.103 ( P = .02). Percent of mast cells expressing TIM-3 in epithelial or stromal layers was not significantly associated with earlier recurrence of polypoid edema. Mast cell burden and TIM-3+ expression were not significantly associated with need for future treatment with steroids post-FESS. Conclusions: Mast cell load in polyp epithelium and stroma may predict a more refractory postoperative course for CRSwNP patients. The role of TIM-3 in the chronic inflammatory state seen in CRSwNP remains unclear.

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.

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