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)

Asthma is a pulmonary inflammatory disease dependent on eosinophil and mast cell infiltration into the lung. CD34 is a sialomucin expressed by both of these cell types, and we have used CD34(-/-) mice and a standard mouse model of asthma to evaluate the importance of CD34 expression on disease development. In comparison with wild-type (wt) mice, CD34(-/-) mice exhibited a dramatic reduction in all hallmarks of allergic asthma, including lowered airway inflammatory cell infiltration, airway hyperresponsiveness, and mast-cell recruitment. Bone marrow transplantation experiments confirmed that these defects are due to CD34 expression by bone marrow-derived cells. This was not, however, due to an inability to respond to antigen as, on a per cell basis, wt and CD34(-/-) inflammatory cells exhibit identical responses in cytokine production. We found a striking reduction in mobility of CD34(-/-) eosinophils in vitro, the major component of inflammatory infiltrates, which was consistent with proposed models for CD34 as an inhibitor of cell-cell adhesion. In summary, our data suggest that CD34 enhances mast-cell and eosinophil invasiveness and that its expression by these cells is a prerequisite for development of allergic asthma.
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PMID:CD34 facilitates the development of allergic asthma. 1755 98

Risk assessment of individuals with anaphylaxis is currently hampered by lack of (1) an optimal and readily available laboratory test to confirm the clinical diagnosis of an anaphylaxis episode and (2) an optimal method of distinguishing allergen-sensitized individuals who are clinically tolerant from those at risk for anaphylaxis episodes after exposure to the relevant allergen. Our objectives were to review the effector mechanisms involved in the pathophysiology of anaphylaxis; to explore the possibility of developing an optimal laboratory test to confirm the diagnosis of an anaphylaxis episode, and the possibility of improving methods to distinguish allergen sensitization from clinical reactivity; and to develop a research agenda for risk assessment in anaphylaxis. Researchers from the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergology and Clinical Immunology held a PRACTALL (Practical Allergy) meeting to discuss these objectives. New approaches being investigated to support the clinical diagnosis of anaphylaxis include serial measurements of total tryptase in serum during an anaphylaxis episode, and measurement of baseline total tryptase levels after the episode. Greater availability of the test for mature beta-tryptase, a more specific mast cell activation marker for anaphylaxis than total tryptase, is needed. Measurement of chymase, mast cell carboxypeptidase A3, platelet-activating factor, and other mast cell products may prove to be useful. Consideration should be given to measuring a panel of mediators from mast cells and basophils. New approaches being investigated to help distinguish sensitized individuals at minimum or no risk from those at increased risk of developing anaphylaxis include measurement of the ratio of allergen-specific IgE to total IgE, determination of IgE directed at specific allergenic epitopes, measurement of basophil activation markers by using flow cytometry, and assessment of allergen-specific cytokine responses. Algorithms have been developed for risk assessment of individuals with anaphylaxis, along with a research agenda for studies that could lead to an improved ability to confirm the clinical diagnosis of anaphylaxis and to identify allergen-sensitized individuals who are at increased risk of anaphylaxis.
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PMID:Risk assessment in anaphylaxis: current and future approaches. 1760 45

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.
Allergy Asthma Proc
PMID:Mediators and cytokines in allergic and viral-triggered rhinitis. 1788 11

The causes of angioedema are not well described, especially in the inpatient setting. The purpose of this study was to examine the causes of moderate to severe angioedema in patients requiring inpatient treatment. We performed a retrospective review in patients requiring inpatient consultation by the Division of Allergy and Immunology at our institution between 1995 and 2004. We focused on potential interactions among medications that elicited life-threatening angioedema requiring intubation. The allergy/immunology service was consulted on 69 patients with moderate to severe angioedema. Medications were the most common cause of angioedema (n = 64, 93%). In most cases (n = 46, 67%), the angioedema was attributed to two or more medications. Patients previously stable on ACE inhibitors (ACEI), aspirin (ASA), or non-steroidal anti-inflammatory drugs (NSAIDs) appeared more likely to develop angioedema soon after the addition of another drug (i.e., ACEI, ASA/NSAIDs, direct mast cell degranulators, and antibiotics). ACEI, ASA/NSAID, and direct mast cell degranulators were contributing causes in 36 patients (56%), 45 patients (70%), and 23 patients (36%), respectively. Twenty patients required intubation, 14 (70%) patients were on ACEI, 12 (60%) patients were on ASA/NSAID, and 7 (35%) patients were on direct mast cell degranulators. ACEI, ASA/NSAID, or direct mast cell degranulators were a cause in 95% (n = 19) of patients requiring intubation. The combination of ACEI and ASA/NSAID was the most frequent cause of angioedema among all patients (n = 17, 25%) and those requiring intubation (n = 8, 40%). Moderate to severe angioedema often is a result of interactions between two or more medications involved in different pathways causing angioedema. In particular, combinations of ACEI, ASA/NSAID, or direct mast cell degranulators may lead to life-threatening angioedema requiring intubation.
Allergy Asthma Proc
PMID:Ten-year study of causes of moderate to severe angioedema seen by an inpatient allergy/immunology consult service. 1830 43

Asthma is an allergic disease characterized by chronic airway eosinophilia and pulmonary infiltration of lymphocytes, particularly of the Th2 subtype, macrophages and mast cells. Previous studies have shown a pivotal role for sphingosine kinase (SphK) on various proinflammatory cells, such as lymphocyte and eosinophil migration and mast cell degranulation. We therefore examined the roles of SphK in a murine model of allergic asthma. In mice previously sensitized to OVA, i.p. administration of N,N-dimethylsphingosine (DMS), a potent SphK inhibitor, significantly reduced the total inflammatory cell infiltrate and eosinophilia and the IL-4, IL-5, and eotaxin levels in bronchoalveolar lavage fluid in response to inhaled OVA challenge. In addition, DMS significantly suppressed OVA-induced inflammatory infiltrates and mucus production in the lungs, and airway hyperresponsiveness to methacholine in a dose-dependent manner. OVA-induced lymphocyte proliferation and IL-4 and IL-5 secretion were reduced in thoracic lymph node cultures from DMS-treated mice. Moreover, similar reduction in inflammatory infiltrates, bronchoalveolar lavage, IL-4, IL-5, eotaxin, and serum OVA-specific IgE levels was observed in mice with SphK1 knock-down via small interfering RNA approach. Together, these data demonstrate the therapeutic potential of SphK modulation in allergic airways disease.
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PMID:The role of sphingosine kinase in a murine model of allergic asthma. 1832 46

Mast cell activation via the high-affinity immunoglobulin (Ig) E receptor Fc epsilon RI is a topic of extensive investigation with therapeutic potential in allergic disease. The protein tyrosine kinases Fyn, Lyn, and Syk are intimately linked with the early events initiated by allergen-mediated aggregation of IgE-occupied Fc epsilon RI. Fyn and Lyn initiate signaling events that are organized by adaptor molecules, which compartmentalize and coordinate the activity of activated protein and lipid kinases and phospholipases to generate lipid products essential for signal amplification and mast cell function. Fyn and Lyn counter-regulate phosphatidylinositol 3-OH kinase (PI3K), controlling the produced amount of phosphatidylinositol (3,4,5)-trisphosphate (PIP3), a key regulator of mast cell degranulation. Fyn and Lyn also activate sphingosine kinases (SphK), which generate sphingosine-1-phosphate (S1P), thus contributing to mast cell chemotaxis and degranulation. Here, we summarize the current knowledge and future challenges and directions.
Curr Allergy Asthma Rep 2008 Mar
PMID:A current understanding of Fc epsilon RI-dependent mast cell activation. 1837 69

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.
Curr Allergy Asthma Rep 2008 Apr
PMID:Upper airways reactions to cold air. 1841 52

Asthma therapy recognizes three fundamental key points: primary prevention, secondary prevention, including the control of inflammatory mechanisms and related symptoms, and tertiary prevention, consisting in the treatment of the early phases leading to airway remodelling. As for primary prevention in infants at ''high risk'' exclusive breastfeeding for at least 3-6 months and the prevention of allergen exposure, respiratory infections and tobacco smoking are recommended. Recent findings suggest a possible protective role of diet (i.e. the intake of vegetables and vitamins and the pre-probiotics). About secondary prevention, the efficacy of drugs suggested by international guidelines (GINA or ARIA) such as antihistamines, leukotriene modifiers and inhaled corticosteroids, it is well known; such drugs can be variably used in different associations, in accordance with the clinical features of the single patient. Among the new therapeutic perspectives, a special attention should be paid to anti-IgE monoclonal antibodies and other humanized monoclonal antibodies targeting and neutralizing inflammatory cytokines; chimeric allergens blocking mast cell receptors; recombinant interleukins with ''anti-inflammatory'' or ''anti-allergic'' properties; in vitro expansion of T lymphocytes with regulatory functions (Treg), and their possible therapeutic approach. Moreover, new experimental observations have identified the role of molecules derived from engineering technologies able to control allergic inflammation. As for prevention and treatment of allergic symptoms, specific immunotherapy has a relevant role, moreover in the paediatric area: it finds progressively greater consensus in terms of both efficacy and safety and is finally recognized in the latest GINA and ARIA guidelines. Tertiary prevention, which concerns the so called ''airway remodeling'', includes new therapeutic approaches such as montelukast, which can control fibroblasts proliferation and their transformation in myofibroblasts, and phosphodiesterase inhibitors. Finally, the use of peptide and non-peptide antagonists of Bradykinin B2 receptors seems to be of great interest.
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PMID:[Future perspectives in the therapy of asthma in children]. 1844 40

Like other inflammatory dermatoses, the pathogenesis of atopic dermatitis (AD) has been largely attributed to abnormalities in adaptive immunity. T helper (Th) cell types 1 and 2 cell dysregulation, IgE production, mast cell hyperactivity, and dendritic cell signaling are thought to account for the chronic, pruritic, and inflammatory dermatosis that characterizes AD. Not surprisingly, therapy has been directed toward ameliorating Th2-mediated inflammation and pruritus. Here, we review emerging evidence that inflammation in AD occurs downstream to inherited and acquired insults to the barrier. Therapy based upon this new view of pathogenesis should emphasize approaches that correct the primary abnormality in barrier function, which drives downstream inflammation and allows unrestricted antigen access.
Curr Allergy Asthma Rep 2008 Jul
PMID:Skin barrier function. 1860 81

Atopic dermatitis (AD) is a complex disease traditionally involving interaction of genetic, environmental, and immunologic factors. Recent studies suggest psycho-neuro-immunologic factors and emotional stress are important in its evolution. The observations that internal (bacterial infections) or external (psycho-logic) stressors may induce AD flares is explained by studies showing that stress impairs the skin barrier function and favors a shift in immunity toward a T helper type 2 cell/allergic response. Furthermore, those with AD appear to have an inherited hypothalamic deficiency that impairs normal hypothalamic-pituitary-adrenal axis function. Neuropeptides released in the skin may also mediate neurogenic inflammation, including mast cell degranulation. AD causes significant stress and impaired quality of life in patients and their family members. Psychologic and stress-reduction interventions were recently shown to improve patient well-being, and to significantly improve cutaneous manifestations.
Curr Allergy Asthma Rep 2008 Jul
PMID:Stress and atopic dermatitis. 1860 83


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