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

The way nasal polyps arise and why they tend to recur is still unknown. Quite frequently they are found in association with asthma, rhinitis and ASA-intolerance, thus suggesting a multifactorial etiopathogenesis. The incidence of atopy in patients affected with nasal polyposis is quite low (16.8%). Recent studies stress the involvement of mast cell mediators due to various degranulating stimuli other than those mediated by IgE. The finding of the interleukin-2 receptor (IL2-R) on murine mast cells and on human peripheral blood basophils, together with the possibility of inducing basophil degranulation through IL2 stimulation, have led the authors to seek IL2R on human nasal polyp mast cells and to study subpopulations of nasal polyp lymphoid infiltrates. Nasal polyps obtained from 4 patients, admitted to the E.N.T. Department of the Catholic University of Rome in 1988, were snap frozen soon after their surgical removal through transmaxillary ethmoidectomy. In this study the following monoclonal antibodies (MoAb) were used: Leu-2a (CD8), Leu-3a/3b (CD4), Leu-4 (CD3), anti-HLA-DR and anti-IL2-R (CD25), OKM1 (CD11), OKB2 (CD24) and 1HT4-4H3 (CD 25). In no patient was there evidence of atopy, asthma or ASA-intolerance. Several mast cells (MC) were observed, chiefly in the connective axis and perivascular areas. These cells were characterized by a large number of cytoplasmatic monomorphic granules. The MC displayed the IL2-R and they were very often close to T-lymphocytes. T-cell subpopulations were predominantly composed of CD4-positive cells (about 75% of all lymphocytes) often associated in clusters and located both in the submucosa and in the connective axis. CD8-positive cells (10-15% of the lymphoid cells) were located most often just under the epithelium. They were hardly ever scattered within the CD4-positive cell clusters. Almost all T cells were activated, above all those surrounding the MC. These results would appear to suggest the presence of a cell-mediated immune response in nasal polyp pathogenesis where MC degranulation, determined by activated T-cell cytokines, plays an important role.
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PMID:[Recent advances concerning etiopathogenesis of nasal polyposis]. 265 69

Nasal polyposis is a chronic inflammatory condition of the upper airways characterized by infiltration of activated inflammatory cells, including mast cells, both in the epithelium and in the stroma. The aim of this work was to study human mast cells derived from two different anatomical sites within the same nasal polyp tissue. To this end, we isolated two distinct mast cell populations, one from the epithelial and the other from the stromal layers of individual human nasal polyp tissues. We examined the mediator content of the two mast cell populations and found that stromal mast cells had a significantly higher content of tryptase compared with the epithelial mast cells from the same tissue. In addition, mast cells from the stromal compartment, but not those from the epithelium, released a significant amount of histamine after anti-IgE stimulation. By contrast, both populations released over 50% of the total histamine after non-specific stimuli (A23187 10(-6) M). The content of mediators and the response to immunological activation were not significantly altered in patients receiving topical steroid therapy. It remains to be determined if the observed differences are the result of an intrinsic characteristic of the mast cell populations localized to separate tissue compartments, or reflect a different in vivo exposure to stimuli such as antigens, or different surrounding structural or infiltrating cells. In conclusion, these data provide evidence of functional heterogeneity and differences in mediator content between mast cell subpopulations from a single human tissue. The failure of release of epithelial mast cell mediators from an immunologic stimulus may have implications concerning acute effects of antigen exposure in nasal polyposis.
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PMID:Functional heterogeneity of mast cells isolated from different microenvironments within nasal polyp tissue. 750 49

Perennial rhinitis and asthma are clinical syndromes representing a range of overlapping pathologies; accurate classification should therefore precede any comparison. Although the sinonasal cavities, trachea and bronchi have a common respiratory mucosa, there are also anatomical differences. For example, the nose has a capacitance vessel network and the lower airways possess smooth muscle, both of which are responsive to neurohumoral influences. The prevalence of rhinitis and asthma has increased over the last three decades. Rhinitis occurs in around 75% of allergic asthmatics while 20% of perennial allergic rhinitics develop asthma. Eosinophils, and their associated proteins and cytokines, may play a central role in both perennial rhinitis and asthma with and without atopy. The characteristic pathology of asthma can be summarized as a chronic, desquamating, eosinophilic bronchitis. Non-allergic rhinitis with eosinophilia is recognized, but without consistent evidence of epithelial damage. Eosinophils are also present in rhinosinusitis with polyposis, particularly in patients with aspirin sensitivity, in whom asthma also often occurs. Increased mast cell activation and mediator release is evident in both perennial rhinitis and asthma following allergen challenge. The importance of mast cells in non-atopic asthma and polyposis is also recognized. Adhesion molecules may also be upregulated, with an increased number and activation of TH2 lymphocytes. However, allergen-resultant T-cell activation may be less marked in the nose than in the lung. Autonomic imbalance also plays a role in both conditions via changes in neural tone to effector tissues, release of neuropeptides, and interplay with cellular recruitment. Pharmacological manipulation of rhinitis and asthma also illustrates the pathological similarities and differences.
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PMID:The link between the nose and lung, perennial rhinitis and asthma--is it the same disease? 921 59

Paranasal sinus mucosa was examined in this study for mast cell membrane-bound IgE. The study material was from 54 patients identified in hospital records as having one of the following diagnoses: chronic sinusitis, chronic sinusitis with asthma, or chronic sinusitis with associated nasal polyps. Formalin-fixed tissue samples taken during endoscopic sinus surgery were routinely processed and examined with hematoxylin and eosin stains. Additional sectioned tissue was analyzed by fluorescence microscopy for mast cells after the use of anti-IgE and anti-tryptase antisera; 45% of the cases of chronic sinusitis, 50% of the cases of chronic sinusitis with polyposis, and 69% of the cases of chronic sinusitis with asthma exhibited 10 or more IgE-positive mast cells in the sinus mucosa. Significant numbers of individuals with chronic sinusitis have coexistent allergic disorders. Some individuals in this study who were not allergic by hospital record review also manifested IgE-positive mast cells in the sinus mucosa; a basis for this finding is proposed.
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PMID:Immunopathologic study of chronic sinusitis: a proposal for atopic and non-atopic IgE-activated mast cell allergic inflammation. 1137 29

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

Aspirin-sensitive asthma is a common and often underdiagnosed disease affecting up to 20% of the adult asthmatic population. It is associated with more severe asthma, requires increased use of inhaled and oral corticosteroids, more presentations to hospital and a risk of life-threatening reactions with aspirin/non-steroid anti-inflammatory drug (NSAID) ingestion. Aspirin-sensitive asthma is often accompanied by severe rhinosinusitis and recurrent nasal polyposis, causing significant impairment of patients' quality of life. The pathogenesis of aspirin-sensitive asthma is complex and involves chronic eosinophilic inflammatory changes, with evidence of increased mast cell activation. The cyclo-oxygenase pathways play a major role in the respiratory reactions that develop after aspirin ingestion. The cysteinyl-leukotrienes have also been shown to play a role in the pathogenesis of aspirin-sensitive asthma. The clinical management of aspirin-sensitive asthma is complicated by the lack of diagnostic testing, other than challenge procedures. Other aspects of management include management of the underlying asthma and avoidance of NSAID in the majority of patients. Other considerations in the management of patients with aspirin-sensitive asthma include the role of leukotriene modifying agents, aspirin desensitization, and the use of other agents, such as roxithromycin. The management of nasal polyposis in patients with aspirin-sensitive asthma often needs to be considered as a separate issue, and requires a team approach.
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PMID:Aspirin-sensitive asthma. 1583 3

In this study, the role of mast and goblet cells and eosinophils in the pathogenesis of nasal polyposis was investigated. The study group consisted of 28 adult patients (15 males, 13 females) with nasal polyposis who underwent functional endoscopic sinus surgery (FESS). All patients in the study group were examined with a questionnaire, an otolaryngologic examination, an endoscopic examination with 0 degrees and 30 degrees endoscopes, Waters' graphy, and axial and coronal computed tomography of the paranasal sinuses. The control group consisted of 10 adult patients without nasal polyp (7 males and 3 females) who underwent septoplasty. They gave written approval to enter the study. The polyp specimens from the study group were excised from four regions: the maxillary sinus, ethmoid sinus, sphenoid sinus, and nasal cavity. They were examined at x400 magnification by light microscopy, and only the slides with polypoid tissue were included in the study. Slides including a chronic inflammatory process without polypoid tissue were excluded from the study. The control group was composed of the slides of specimens from the inferior turbinate. Forty slides (10 in each group) in the study group and 10 slides in the control group were included in the study. The surgical specimens from the study and control groups were examined with a histochemical staining technique. In every surgical specimen, the type of epithelium and the numbers of goblet and mast cells and eosinophils were calculated in x400 high-magnification field in 10 areas on light microscopy, as well as the mean number of these cells, and for mast cells separately, cell count in the epithelium and the stromal layer of polyp tissue and total mast cell count, including both epithelial and stromal mast cells, were identified. Goblet cells, mast cells, and inflammation with eosinophils were observed in all sinonasal mucosa. The common epithelial type in the polyp tissue was pseudostratified ciliated cylindric epithelium, which contains goblet cells. Goblet cell numbers in the maxillary, ethmoid, and sphenoid sinuses and nasal cavity were found to be significantly higher than in the control group (p < .05). For total mast cell and eosinophil count, no statistically significant difference was found between all five groups. In each group, there was no statistically significant difference between goblet and mast cells. Increased goblet cells in sinonasal polyps indicated that systemic factors also affect nasal polyposis as much as local factors, such as airflow and mucosal contact. Surgical treatment of sinonasal polyps by FESS causes more sufficient air ventilation in the nasal cavity and paranasal sinuses. Therefore, the goblet cell density will decrease because of the exposure of the mucosal surfaces to the air. In particular, FESS and then the appropriate medical treatment may decrease the recurrence rates and increase the patient's comfort. The significantly increased goblet cell count in the sinonasal mucosa demonstrated the importance of these cells in the pathogenesis of nasal polyposis. Also, mast cells and eosinophils may have a role in the inflammatory processes, leading to nasal polyposis formation.
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PMID:Role of mast and goblet cells in the pathogenesis of nasal polyps. 1652 32

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

Gounaris and colleagues describe a previously unrecognized cross-talk between mast cells and Treg in colon adenomatous polyposis (Gounaris et al., Cancer Res 2009;69:5490-7). Adoptively transferred Treg suppress the focal mastocytosis that fosters tumor initiation and progression. In contrast, endogenous Treg, which abundantly infiltrate polyps, show proinflammatory activity under unknown microenvironmental cues that promote mast cell differentiation and expansion. Compartmentalized Treg plasticity seems to be a key factor in establishing the optimal milieu for cancer development in the intestines. Treg partnership with mast cells recapitulates the complexity of innate-adaptive networks characterizing gut inflammation and represents a novel target for cancer immunotherapy.
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PMID:Polyps wrap mast cells and Treg within tumorigenic tentacles. 1957 Jul 83

Aspirin-sensitive respiratory disease (ASRD) is a condition characterized by persistent and often severe inflammation of the upper and lower respiratory tracts. Patients develop chronic eosinophilic rhinosinusitis, nasal polyposis, and asthma. The ingestion of aspirin and other cyclooxygenase-1 (COX-1) inhibitors induces exacerbations of airway disease that may be life-threatening. Thus, aspirin sensitivity is a phenotypic marker for the syndrome, yet nearly all affected individuals can be desensitized by the administration of graded doses of aspirin, leading to long-term clinical benefits. Patients with aspirin sensitivity are often able to tolerate selective COX-2 inhibitors. The pathogenesis of ASRD is underpinned by abnormalities in eicosanoid biosynthesis and eicosanoid receptor expression coupled with intense mast cell and eosinophilic infiltration of the entire respiratory tract. This review focuses on the molecular, cellular, and biochemical abnormalities characterizing ASRD and highlights unanswered questions in the literature and potential future areas of investigation.
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PMID:Aspirin-sensitive respiratory disease. 1957 83


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