Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allergic rhinitis triggers a systemic increase of inflammation. Within minutes of allergen exposure, immune cells release histamine, proteases, cysteinyl leukotrienes, prostaglandins, and cytokines. Some produce the early symptoms, while others augment the production, systemic circulation, and subsequent infiltration of the nasal mucosa with inflammatory cells that sustain the symptoms. Systemic circulation of inflammatory cells permits their infiltration into other tissues where chemoattractant and adhesion molecules already exist. Consequently, allergic rhinitis is linked to comorbid conditions: asthma, chronic hyperplastic eosinophilic sinusitis, nasal polyposis, and serous otitis media. Effective therapy should be directed at underlying inflammation and its systemic manifestations. It should improve the rhinitis and the comorbid conditions. Antihistamines relieve early symptoms by blocking basophil- and mast cell-generated histamine, but they do not significantly influence the pro-inflammatory loop. They are often little better than placebo. Oral corticosteroids provide the systemic anti-inflammatory efficacy, but their toxicity precludes such an approach. Intranasal corticosteroids effectively target the local inflammatory processes of rhinitis, reducing local inflammatory cells within the nares, but they do not directly access tissues involved in the comorbid conditions. Leukotriene modifiers have both systemic anti-inflammatory effects and an acceptable safety profile.
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PMID:Allergic rhinitis: systemic inflammation and implications for management. 1465 51

Mast cells play a key role in the induction of allergic disorders, such as asthma and rhinitis, through the release of mediators including histamine, arachidonate products, proteases and several cytokines, which are found in relatively high quantities in these cells. A significant number of therapeutic approaches for allergies have been designed based on antagonising specific mediators released from mast cells and on selectively inhibiting the activation of these cells. Classical mast cell stabilisers, such as sodium cromoglycate, continue to attract new developments based on improved formulation and delivery systems, while efforts to identify new pathway (e.g., tyrosine kinase Syk) inhibitors or mediator (e.g., prostaglandin D2, beta-tryptase) antagonists may bring new successes to this field.
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PMID:Targeting mast cells. 1521 15

Conventional knowledge tells us that mast cells are only important in the acute IgE-mediated reactions as seen in anaphylaxis, asthma and rhinitis. Yet, in recent years, much evidence has accumulated on the versatile role of mast cells in allergic inflammation. Here, we describe the novel and potential roles of mast cells in the late phase allergic reaction as well as in chronic allergic inflammation. Mast cells in patients with allergic rhinitis and asthma produce Th2 type cytokines, induce IgE synthesis in B cells and can autoactivate itself via the mast cell-IgE-FcepsilonRI cascade. In addition, mast cells upregulate the production of a variety of cytokines/chemokines in epithelial cells and fibroblasts and induce the recruitment of basophils, T cells and eosinophils into sites of allergic inflammation as well as their own intraepithelial accumulation. Furthermore, mast cells express MMPs and interact with extracellular matrix proteins and ASM and may play a role in nasal and bronchial hyperresponsiveness as well as tissue remodelling. In chronic rhinosinusitis with nasal polyps, the potential role of mast cells not only in orchestrating eosinophilic inflammation but also in the genesis and perpetuation of nasal polyp formation via FcepsilonRI and TLR mediated activation is also of growing interest.
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PMID:Mast cells in allergic airway disease and chronic rhinosinusitis. 1610 67

The upper airway occupies a sentinel position with respect to the physical and chemical qualities of the inspired atmosphere. Responses of the upper airway can be acute or chronic, as well as primary (sensory) or secondary (physiologic). Olfaction and sensory irritation are cofactors in the perception of air quality. Secondary reflex responses to airborne irritants may include blockage (airflow obstruction), secretion (with or without associated inflammation), and alterations in mucociliary clearance. Of the above end points, obstruction has been documented in response to a variety of agents, including acetic acid vapor, ammonia, Cl2, ETS, mixed VOCs, vapors from carbonless copy paper, and (variably) SO2. Alterations in mucociliary clearance have been variably observed with SO2 and ETS exposure. A neutrophilic inflammatory response has been documented after acute exposure to either ozone or VOCs, and metaplastic mucosal changes after prolonged exposures to photochemical mixed air pollutants. Augmented reactivity to irritants is a phenotypic characteristic of both nonallergic and allergic rhinitis; however, understanding of underlying mechanisms remains elusive (75-78). Differential physiologic responsiveness to environmental irritant stimuli has been documented by allergic rhinitis status for acetic acid and Cl2 (objectively) and for mixed VOCs (subjectively only). Differential responsiveness by nonallergic rhinitis status has, to our knowledge, been documented for paper dust only, although a somewhat wider array of pollutants (including ETS and carbonless copy paper) has been studied in groups differing by self-reported pollutant reactivity. Interestingly, although the congestive response to allergens and irritants is similar, the underlying mechanisms appear to differ, with neither mast cell degranulation nor cholinergic parasympathetic reflexes appearing critical to the response (Fig. 3). Although neuropeptide release does not accompany Cl2-induced nasal obstruction, in one model system (hypertonic saline challenge), substance P release accompanied augmented secretions (80,81). In yet another hypertonic model (dry mannitol powder challenge), arachidonic acid metabolites characteristic of epithelial cell activation accompanied nasal obstruction (82). The relevance of these model systems to environmentally realistic (airborne) irritants remains unclear at this time. Overall, nonallergic rhinitis has received considerably less attention than has allergic rhinitis in the context of descriptive, pathophysiologic, and intervention studies. This statement applies equally in the context of environmental nonallergic rhinitis. As is hopefully evident from the above discussion, many potential research questions in this area remain to be addressed.
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PMID:Environmental nonallergic rhinitis. 1715 18

Intermittent allergic rhinitis and common cold constitute frequent conditions and show similar clinical symptoms. The purpose of this study was to investigate the pattern of cytokines in the nasal fluid of patients with acute symptoms caused by allergic and viral rhinitis. Nasal secretions were analyzed by immunosorbent assay techniques using a cytokine panel assay and routine ELISA. Allergic patients had significantly higher levels of eosinophil cationic protein (ECP), interleukin (IL)-5, and tryptase. Significantly elevated concentrations of proinflammatory cytokines (IL-1b, IL-6, IL-7, IL-17, interferon [IFN] gamma, and tumor necrosis factor [TNF]-alpha) as well as chemokines for cellular infiltration (IL-8, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1beta), factors for cellular proliferation (granulocyte colony-stimulating factor [G-CSF] and granulocyte macrophage colony-stimulating factor [GM-CSF]), and elastase were found in viral rhinitis. IL-10 was only detectable in viral rhinitis. IL-4 was significantly higher in patients with viral rhinitis than allergic rhinitis, and IL-5 was significantly elevated in viral rhinitis compared with controls. In viral-triggered rhinitis, we detected a predominantly Th1-type cytokine pattern with potent proinflammatory mediators. Factors reflecting a neutrophil and eosinophil immune response, due to IL-5, IL-8, GM-CSF, ECP, and elastase were shown. Nasal secretions of patients with allergic rhinitis showed highest concentrations of tryptase, IL-5, and ECP, reflecting a mast cell and eosinophil immune response. Nasal secretion levels of IL-4 did not show highest levels in allergic rhinitis but did in viral rhinitis. IL-4 also may play a role in limiting inflammatory processes by inhibiting the production of inflammatory cytokines.
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PMID:Mediators and cytokines in allergic and viral-triggered rhinitis. 1788 11

Cold air-induced rhinitis is a common complaint of individuals with chronic allergic or nonallergic rhinitis and those with no chronic nasal disease. It is characterized by rhinorrhea, nasal congestion, and nasal burning that appear within minutes of exposure to cold air and dissipate soon after exposure is terminated. The symptoms of cold-air rhinitis are reproduced experimentally with nasal cold-air provocation. This procedure has shown that nasal mast cell activation and sensory nerve stimulation are associated with the development of nasal symptoms. Sensory nerve activation generates a cholinergic reflex that leads to rhinorrhea; therefore, anticholinergic agents are highly effective in treating cold-air rhinitis. Experimental data suggest that individuals with nasal cold-air sensitivity may have reduced ability to compensate for the water loss that occurs during exposure to cold air. Therefore, the symptoms of cold air-induced rhinitis may reflect the activation of compensatory mechanisms to restore mucosal homeostasis.
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PMID:Upper airways reactions to cold air. 1841 52

Ovalbumin-induced guinea pig model of rhinitis was assessed for its utility in the studies of rhinitis. Systemic sensitization and challenge with ovalbumin-induced rhinitis symptoms and an increase in anti-OVA-IgE and IgG titers, positive skin reactions and nasal lavage IL-4 concentration. Histopathology of nasal mucosa showed infiltration of eosinophils and other inflammatory cells consistent with the symptoms. Topical sensitization of ovalbumin yielded inconsistent symptoms of rhinitis. In systemic sensitization model, repeated challenge of ovalbumin caused similar response for at least 3 consecutive challenges. The symptoms were affected by relative humidity in the air and dosing volume of topical drugs. Sneezing and lacrimation were reduced by acute oral administration of the H1 receptor antagonists and steroids or the prophylactic oral administration of cysteinyl leukotriene (CysLT1) receptor antagonist montelukast or acute topical antihistamines, mast cell stabilizer sodium cromoglycate and anticholinergic agent ipratropium bromide, but not by a topical steroid. Nose rubbing was reduced significantly by some oral and topical antihistamines. Oral steroids offered excellent protection against all symptoms. Dexamethasone and montelukast also inhibited nasal lavage IL-4 concentration and inflammatory cell infiltration. Treatment with topical steroid fluticasone for 2 weeks had no effect on sneezing or rubbing. However, it caused complete inhibition of congestion. The cyclooxygenase inhibitor indomethacin had no effect on symptoms of rhinitis. The adrenergic alpha receptor agonist-decongestant oxymetazoline caused reduction in congestion. These results suggest that differential responsiveness to symptoms of rhinitis by a new agent can be very well profiled in the model in congruence with the mediation pathways and mechanism of action of drugs. The model provides complete symptomatic characterization of rhinitis and is a good tool for its study.
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PMID:Validation of guinea pig model of allergic rhinitis by oral and topical drugs. 1862 97

The ability of Staphylococcus aureus to invade and survive within host cells is believed to contribute to its propensity to cause persistent and metastatic infections. In addition, S. aureus infections often are associated with atopic diseases such as dermatitis, rhinitis, and asthma. Mast cells, the key cells of allergic diseases, have a pivotal role in innate immunity and have the capacity of phagocytosis, and they can destroy some pathogenic bacteria. However, little is known about the ability of some other bacteria to survive and overcome mast cell phagocytosis. Therefore, we were interested in evaluating the interplay between mast cells and S. aureus. In this study, we show that human cord blood-derived mast cells (CBMC) can be infected by pathogenic S. aureus. S. aureus displayed a high adherence to mast cells as well as invasive and survival abilities within them. However, when infections were performed in the presence of cytochalasin D or when CBMC were preincubated with anti-Toll-like receptor 2 (TLR2) or anti-CD48 antibodies, the invasiveness and the inflammatory response were abrogated, respectively. Furthermore, we observed an increase of TLR2 and CD48 molecules on CBMC after S. aureus infection. The infection of CBMC with S. aureus also caused the release of tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8). Both live and killed S. aureus organisms were found to trigger TNF-alpha and IL-8 release by CBMC in a time-dependent manner. Cumulatively, these findings suggest that S. aureus internalizes and survives in mast cells. This may play an important role in infections and in atopic diseases associated with S. aureus.
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PMID:Human mast cell activation by Staphylococcus aureus: interleukin-8 and tumor necrosis factor alpha release and the role of Toll-like receptor 2 and CD48 molecules. 1864 75

Mast cells are key components of the immune system, where they help orchestrate the inflammatory response. Aberrant mast cell activation is linked to a variety of allergic diseases, including asthma, eczema, rhinitis, and nasal polyposis, which in combination affect up to 20% of the population in industrialized countries. On activation, mast cells release a variety of signals that target the bronchi and vasculature and recruit other immune cells to the inflammatory site. Prominent among such signals are the cysteinyl leukotrienes, a family of potent proinflammatory lipid mediators comprising leukotriene C(4) (LTC(4)), LTD(4), and LTE(4). LTC(4), the parent compound, is secreted from mast cells following Ca(2+) influx through store-operated calcium release-activated calcium (CRAC) channels. Here, we show that activated mast cells release a paracrine signal that evokes Ca(2+) signals in spatially separate resting mast cells. The paracrine signal was identified as a cysteinyl leukotriene because 1) RNAi knockdown or pharmacological block of the 5-lipoxygenase enzyme prevented activated mast cells from stimulating resting cells. 2) Block of cysteinyl leukotriene type I receptors on resting mast cells with the clinically prescribed receptor antagonist montelukast prevented their activation by active mast cells. 3) RNAi knockdown of cysteinyl leukotriene type I receptors on resting cells prevented them from responding to the paracrine signal derived from activated mast cells. 4) Purified LTC(4) evoked Ca(2+) signals in mast cells that were identical to those triggered by the paracrine signal. Low levels of stimulus intensity released sufficient levels of leukotriene to activate resting cells. Leukotriene secretion still occurred tens of minutes after stimulation, suggesting a role as a long-lasting trigger in mast cell activation. Stimulation of the cysteinyl leukotriene receptor activated CRAC channels and evoked prominent store-operated Ca(2+) entry. This resulted in further cysteinyl leukotriene production, triggering a positive feedback cascade. Acutely isolated mast cells from patients with allergic rhinitis exhibited store-operated Ca(2+) influx through CRAC channels and responded to cysteinyl leukotrienes. Histological analysis of samples taken from patients revealed clustering of mast cells, often located within 20 microm of each other, a distance sufficient for paracrine signaling by leukotrienes to operate effectively. We conclude that a positive-feedback cascade involving CRAC channels and cysteinyl leukotrienes constitute a novel mechanism for sustaining mast cell activation.
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PMID:Intercellular Ca2+ wave propagation involving positive feedback between CRAC channels and cysteinyl leukotrienes. 1897 54

Nasal cytology represents a valid method in the differential diagnosis of allergic and non-allergic nasal diseases, as it is simple, safe, non-invasive, cost-effective, and easy to perform both in the medical and paediatric office. In particular, through cytological investigation it is possible to diagnose a group of non-allergic infective rhinitis that still today constitutes a vague aspect of the clinical-diagnostic-therapeutic approach to eosinophilic non-allergic rhinitis (NARES), non-allergic rhinitis mast cell (NARMA), neutrophilic non-allergic rhinitis (NARNA), and eosinophil-mast cell non-allergic rhinitis (NARESMA). Preventive treatment of nasal diseases, when guided by rhinocytograms, leads to a favorable clinical and time-dependent outcome. These advantages are reflected in a better quality of life and in a reduction in National Health Service costs, without chronic evolution of the disease to complications.
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PMID:Role of nasal cytology. 2015 80


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