Mast cells

1997 ◽  
Vol 77 (4) ◽  
pp. 1033-1079 ◽  
Author(s):  
D. D. Metcalfe ◽  
D. Baram ◽  
Y. A. Mekori
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Tissue Repair ◽  
Defense Mechanisms ◽  
Cell Activation ◽  
Allergic Inflammation ◽  
Local Environment ◽  
The Body ◽  
Mast Cell Activation ◽  
Biological Functions

Mast cells are found resident in tissues throughout the body, particularly in association with structures such as blood vessels and nerves, and in proximity to surfaces that interface the external environment. Mast cells are bone marrow-derived and particularly depend upon stem cell factor for their survival. Mast cells express a variety of phenotypic features within tissues as determined by the local environment. Withdrawal of required growth factors results in mast cell apoptosis. Mast cells appear to be highly engineered cells with multiple critical biological functions. They may be activated by a number of stimuli that are both Fc epsilon RI dependent and Fc epsilon RI independent. Activation through various receptors leads to distinct signaling pathways. After activation, mast cells may immediately extrude granule-associated mediators and generate lipid-derived substances that induce immediate allergic inflammation. Mast cell activation may also be followed by the synthesis of chemokines and cytokines. Cytokine and chemokine secretion, which occurs hours later, may contribute to chronic inflammation. Biological functions of mast cells appear to include a role in innate immunity, involvement in host defense mechanisms against parasitic infestations, immunomodulation of the immune system, and tissue repair and angiogenesis.

Abstract 15720: Transmembrane Stem Cell Factor Delivered in Nanocarriers Promotes Angiogenesis in Ischemia Without Mast Cell Activation

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Eri Takematsu ◽  
Sanjana Srinath ◽  
Michael Sherman ◽  
Andrew K Dunn ◽  
Aaron Baker
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Mast Cells ◽  
Stem Cell Factor ◽  
Cell Activation ◽  
The Body ◽  
Mast Cell Activation ◽  
Protein Therapy ◽  
Current Standard ◽  
Therapeutic Benefits

Introduction: The current standard cares for peripheral artery disease (PAD) include surgical revascularizations with bypass grafting or percutaneous interventions. However, these interventions cannot be performed in a significant portion of patients, and many do not respond to these surgical procedures. Protein therapy to stimulate the body to create new vasculature is another alternative, which is minimally invasive to patients. Stem cell factor (SCF) is a candidate protein for treating PAD, but clinical use of SCF has been limited due to toxicity related to mast cell activation. SCF also exists in a transmembrane form (tmSCF), possessing differential activities from soluble SCF and has not been explored as a therapeutic agent. Results: To develop tmSCF as a therapeutic we created tmSCF embedded in liposome or lipid nanodisc (Fig. A) . Hindlimb ischemia model on WT and ob/ob mice showed that tmSCF proteliposome (tmSCFPL) and nanodisc (tmSCFND) improved blood flow recovery significantly more than control (Fig. B, C) . Mouse model of anaphylaxis revealed that tmSCF-based therapies did not activate mast cells (Fig. D, E) . Colocalization assay of c-Kit and clathrin/caveolin revealed that mast cells preferentially use clathrin-mediated pathways to internalize SCF and caveolin-mediated pathways for tmSCF-based therapies (Fig. F, G) . Surface c-Kit internalization study on mast cells showed faster uptake of SCF in comparison to tmSCF-based therapies (Fig. H) . Previous study indicates that clathrin-mediated internalization causes increased activation of mast cells. Our studies together with the previous finding suggest that mast cell activation does not occur for tmSCF-based therapies because of the slower uptake, greater utilization of the caveolin internalization pathway and weaker activation of mast cells. Conclusions: TmSCF-based therapies can provide therapeutic benefits without off-target effects on mast cells by tuning activation with nanocarriers.

scholarly journals Anaplasma phagocytophilum Infects Mast Cells via α1,3-Fucosylated but Not Sialylated Glycans and Inhibits IgE-Mediated Cytokine Production and Histamine Release

2011 ◽  
Vol 79 (7) ◽  
pp. 2717-2726 ◽  
Author(s):  
Nore Ojogun ◽  
Brian Barnstein ◽  
Bernice Huang ◽  
Carole A. Oskeritzian ◽  
Jonathon W. Homeister ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Anaplasma Phagocytophilum ◽  
Defense Mechanisms ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Murine Bone Marrow ◽  
Granulocytic Anaplasmosis

ABSTRACTMast cells are sentinels for infection. Upon exposure to pathogens, they release their stores of proinflammatory cytokines, chemokines, and histamine. Mast cells are also important for the control of certain tick-borne infections.Anaplasma phagocytophilumis an obligate intracellular tick-transmitted bacterium that infects neutrophils to cause the emerging disease granulocytic anaplasmosis.A. phagocytophilumadhesion to and infection of neutrophils depend on sialylated and α1,3-fucosylated glycans. We investigated the hypotheses thatA. phagocytophiluminvades mast cells and inhibits mast cell activation. We demonstrate thatA. phagocytophilumbinds and/or infects murine bone marrow-derived mast cells (BMMCs), murine peritoneal mast cells, and human skin-derived mast cells.A. phagocytophiluminfection of BMMCs depends on α1,3-fucosylated, but not sialylated, glycans.A. phagocytophilumbinding to and invasion of BMMCs do not elicit proinflammatory cytokine secretion. Moreover,A. phagocytophilum-infected cells are inhibited in the release of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-13, and histamine following stimulation with IgE or antigen. Thus,A. phagocytophilummitigates mast cell activation. These findings potentially represent a novel means by whichA. phagocytophilumusurps host defense mechanisms and shed light on the interplay between mast cells and vector-borne bacterial pathogens.

scholarly journals Intestinal Mucosal Mast Cells: Key Modulators of Barrier Function and Homeostasis

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 135 ◽  
Author(s):  
Mercé Albert-Bayo ◽  
Irene Paracuellos ◽  
Ana M. González-Castro ◽  
Amanda Rodríguez-Urrutia ◽  
María J. Rodríguez-Lagunas ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Cell Activity ◽  
Intestinal Barrier ◽  
The Body ◽  
Mast Cell Activation ◽  
Mucosal Barrier ◽  
Mucosal Mast Cell

The gastrointestinal tract harbours the largest population of mast cells in the body; this highly specialised leukocyte cell type is able to adapt its phenotype and function to the microenvironment in which it resides. Mast cells react to external and internal stimuli thanks to the variety of receptors they express, and carry out effector and regulatory tasks by means of the mediators of different natures they produce. Mast cells are fundamental elements of the intestinal barrier as they regulate epithelial function and integrity, modulate both innate and adaptive mucosal immunity, and maintain neuro-immune interactions, which are key to functioning of the gut. Disruption of the intestinal barrier is associated with increased passage of luminal antigens into the mucosa, which further facilitates mucosal mast cell activation, inflammatory responses, and altered mast cell–enteric nerve interaction. Despite intensive research showing gut dysfunction to be associated with increased intestinal permeability and mucosal mast cell activation, the specific mechanisms linking mast cell activity with altered intestinal barrier in human disease remain unclear. This review describes the role played by mast cells in control of the intestinal mucosal barrier and their contribution to digestive diseases.

scholarly journals Rno-miR-199a-3p targets Nedd4 to promote sensitization of ST36 acupoints via mast cell activation in a rat model of knee osteoarthritis

2021 ◽  
Author(s):  
Wenchuan Qi ◽  
Baitong Liu ◽  
Yilu Jiang ◽  
Xinye Luo ◽  
Zhiwei Li ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Knee Osteoarthritis ◽  
Histamine Release ◽  
Rat Model ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Ectopic Expression ◽  
The Body ◽  
Mast Cell Activation

Abstract Selecting routine points on related meridians is widely accepted as the foundational principle of acupuncture. When the body is suffering disease or injury, corresponding acupoints are thought to be activated and manifest in several sensitized forms. Sensitized acupoints hold high clinical value as a reflection of disease activity on the body surface. Mast cells have been implicated in the process of acupoint sensitization but the underlying regulatory mechanisms remain unclear. In the present study, we evaluated ST36 as a sensitized acupoint in the monosodium iodoacetate-induced knee osteoarthritis rat model. We first confirmed sensitization at the ST36 acupoint through decreases in the acupoint mechanical pain threshold and instructively found an accompanying increase in skin mast cell degranulation. Thereafter, we used highthroughput RNA sequencing to reveal potential molecular mechanisms of acupoint sensitization. We showed that rno-miR-199a-3p was highly expressed in the sensitized ST36 acupoint and its expression was associated with mast cells. Functional experiments revealed that overexpression of rno-miR-199a-3p increased mast cell histamine release whereas inhibition of rno-miR-199a-3p decreased histamine release. Mechanistically, we established rno-miR-199a-3p acted to inhibit neural precursor cell expressed developmentally down-regulated 4 (Nedd4) protein expression through miRNA-mediated targeting of the 3’-UTR of Nedd4 mRNA. Moreover, we found ectopic expression of Nedd4 antagonized histamine release in mast cells and blocked the actions of rno-miR-199a-3p overexpression. Thus, our study establishes that mast cells participate in the process of acupoint sensitization, and further reveals a novel miRNA-based mechanism which is crucial for further understanding of acupoint sensitization and acupuncture applications.

scholarly journals Mast Cell Activation Disorders

Medicina ◽  
2021 ◽  
Vol 57 (2) ◽  
pp. 124
Author(s):  
Arianna Giannetti ◽  
Emanuele Filice ◽  
Carlo Caffarelli ◽  
Giampaolo Ricci ◽  
Andrea Pession
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Clinical Manifestations ◽  
The Body ◽  
Mast Cell Activation ◽  
Detailed Knowledge ◽  
Pediatric Age ◽  
Mast Cell Activation Syndrome ◽  
Activation Syndrome

Background and Objectives: Mast cell disorders comprise a wide spectrum of syndromes caused by mast cells’ degranulation with acute or chronic clinical manifestations. Materials and Methods: In this review article we reviewed the latest findings in scientific papers about mast cell disorders with a particular focus on mast cell activation syndrome and mastocytosis in pediatric age. Results: Patients with mast cell activation syndrome have a normal number of mast cells that are hyperreactive upon stimulation of various triggers. We tried to emphasize the diagnostic criteria, differential diagnosis, and therapeutic strategies. Another primary mast cell disorder is mastocytosis, a condition with a long-known disease, in which patients have an increased number of mast cells that accumulate in different regions of the body with different clinical evolution in pediatric age. Conclusions: Mast cell activation syndrome overlaps with different clinical entities. No consensus was found on biomarkers and no clearly resolutive treatment is available. Therefore, a more detailed knowledge of this syndrome is of fundamental importance for a correct diagnosis and effective therapy.

scholarly journals MicroRNA Involvement in Allergic and Non-Allergic Mast Cell Activation

2019 ◽  
Vol 20 (9) ◽  
pp. 2145 ◽  
Author(s):  
Irit Shefler ◽  
Pazit Salamon ◽  
Yoseph A. Mekori
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Inflammatory Diseases ◽  
Allergic Inflammation ◽  
Mast Cell Activation ◽  
Therapeutic Approaches ◽  
Coordinated Expression ◽  
And Function

Allergic inflammation is accompanied by the coordinated expression of numerous genes and proteins that initiate, sustain, and propagate immune responses and tissue remodeling. MicroRNAs (miRNAs) are a large class of small regulatory molecules that are able to control the translation of target mRNAs and consequently regulate various biological processes at the posttranscriptional level. MiRNA profiles have been identified in multiple allergic inflammatory diseases and in the tumor microenvironment. Mast cells have been found to co-localize within the above conditions. More specifically, in addition to being essential in initiating the allergic response, mast cells play a key role in both innate and adaptive immunity as well as in modulating tumor growth. This review summarizes the possible role of various miRNAs in the above-mentioned processes wherein mast cells have been found to be involved. Understanding the role of miRNAs in mast cell activation and function may serve as an important tool in developing diagnostic as well as therapeutic approaches in mast cell-dependent pathological conditions.

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.

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.

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