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)

IgE is a homocytotropic antibody which binds to the surface of the mast cell. Antigen with affinity for IgE triggers conformational change at the cell surface, resulting in the release of chemical mediators from the mast cell granules. The mediators histamine, slow reacting substance of anaphylaxis and eosinophil chemotactic factor cause smooth muscle contraction, increased capillary permeability, eosinophil attraction and increased glandular secretions. The release of mediators from the mast cell granules is controlled by intracellular levels of cyclic nucleotides. In particular, elevated cyclic AMP inhibits mediator release. Adrenergic, cholinergic and prostaglandin receptors all influence mediator release. The characteristic immunopathology of immediate hypersensitivity reactions is a result of local or systemic mediator release. Such reactions include anaphylaxis, asthma, allergic rhinitis, urticaria and angioedema. Similar immunopathology may sometimes result from mechanisms not involving IgE or histamine mediators. Routine investigation of patients with immediate hypersensitivity should include eosinophil counts and IgE levels in blood and secretions, and immediate hypersensitivity skin tests. RAST testing is not routine. Therapeutic principles of these reactions include restoration of inhibitory levels of cyclic nucleotides, antagonism of mediator effects and immunological manipulation of the IgE mediated allergic reaction.
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PMID:The immunological basis of immediate hypersensitivity. 8 47

Hyperplasia of mucosal mast cells (MMC) is found in many enteropathies which are caused by T lymphocytes, but their exact role is unknown. In this study we have investigated whether MMC play a part in the immunologically mediated enteropathy which occurs in mice with graft-versus-host reaction (GvHR). There were simultaneous increases in the numbers of jejunal MMC and in the concentrations of mouse intestinal mast cell proteinase both in serum and in the intestine in two separate models of GvHR. Although these changes developed in parallel with the evolving GvHR, there was no correlation between the degree of MMC activation and the severity of the intestinal pathology. In addition, mast cell deficient W/Wv mice developed systemic and intestinal GvHR as severe as their normal congenic littermates, despite a markedly deficient MMC response. We conclude that the role of MMC in enteropathy may be to regulate or repair T lymphocyte mediated immunopathology.
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PMID:Role of mucosal mast cells in intestinal graft-versus-host reaction in the mouse. 210 Nov 24

Because of the tremendous impact that parasitic infections have on the health and productivity of humans and domestic animals, considerable research effort has been focused upon understanding the mechanisms of host-parasite coexistence, host resistance and immunopathology. Studies have employed a range of approaches including: kinetic analysis of parasite establishment, development, fecundity and survival in naive and previously-infected hosts; correlation between parasite survival and histopathologic responses at the site of infection; vaccination with attenuated parasites or their products; cellular and serum transfer of immunity to naive or immunocompromised hosts; pharmacologic manipulation of potential mediators of host defense using agonistic and antagonistic drugs. However, it is becoming increasingly clear that to understand the mechanisms associated with host resistance and parasite survival, one must define the characteristics of the local microenvironment at the host-parasite interface. One of the approaches by which such studies can be made involves the isolation and characterization of cells derived from the local infection site. This manuscript reviews some of these studies on local aspects of mucosal immune responses in parasitic infections. Examples that will be discussed include IgA antibody, intraepithelial leukocytes from the intestine, intestinal mast cell populations, macrophages derived from bronchoalveolar lavage, and local immunoregulatory responses during respiratory and intestinal parasitic infection. These studies have established unequivocally that local responses to mucosal parasitic infection can only be appropriately investigated using cells derived from the specific microenvironment. This conclusion should encourage others to further study these local responses and to be innovative in investigating unexplored aspects of the host-parasite interface.
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PMID:Unique characteristics of local responses in host resistance to mucosal parasitic infections. 351 14

Eleven female patients with adult-onset Still's disease were followed for 7-36 years (mean 20.2 years) after the onset of their illness. Ten of these patients had a chronic course characterized by remissions and exacerbations of arthritis associated with fever and rash. Five patients had terminal interphalangeal involvement, and carpal ankylosis was demonstrated on x-ray film in 10. Two patients developed a widespread polyarthritis, and renal amyloidosis was diagnosed 10 years after disease onset in the most severely affected patient. In 4 patients studied during an exacerbation of the disease, circulating immune complexes were detected by the staphylococcal A binding assay, but not by the C1q binding assay. Synovial fluid analysis in 1 patient revealed a low C3 level and total hemolytic complement (CH50) together with immune complexes and IgG rheumatoid factor. Immune complexes were not identified in the characteristic Still's rash by immunofluorescence or electron microscopy, although mast cell degranulation, neutrophil lysis, and perivascular fibrin deposition were reminiscent of immune complex--mediated vascular injury. The clinical and laboratory features as well as the long-term course of adult- and juvenile-onset systemic Still's disease are similar, but further studies of genetic markers and immunopathology are required to establish a common pathophysiology.
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PMID:Adult-onset Still's disease. Twenty-year followup and further studies of patients with active disease. 709 64

Immuno-histopathological studies of conjunctival tissue biopsied from patients with non-sight-threatening allergic conjunctivitis or with sight-threatening allergic keratoconjunctivitis should lead to more effective management of these eye conditions, based on the specific cellular involvement. The major difference between these two categories of eye disease was the occurrence of T-lymphocytes, which were absent in the former but prominent in the sight-threatening disorders. Seasonal and perennial allergic conjunctivitis both showed a heavy mast cell increase, due to infiltration of mucosal type mast cells, and allergen challenge studies linked mast cell histamine release to the early phase reaction occurring within 20 minutes. A second histamine peak at six hours after challenge might implicate basophils (or refractory mast cells) and was accompanied by a rise in eosinophil cationic protein. In sight-threatening, chronic allergic keratoconjunctivitis the responses were clearly directed by T-cells, themselves the primary effector cell in atopic keratoconjunctivitis, whereas vernal keratoconjunctivitis displayed a T-cell driven eosinophilia, with increased expression of the adhesion molecules involved in tissue invasion by these cells. Appropriate therapies for each different category of conjunctivitis should be based on the specific immunopathology, and directed at the activated cell types that are primarily responsible for the disease process.
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PMID:Therapeutic considerations: symptoms, cells and mediators. 754 Mar 64

It has been proposed that a specific IgE response contributes to the immunopathology of acute respiratory syncytial virus (RSV) bronchiolitis but previous work has been difficult to replicate. Indirect evidence that might support this contention was sought by measuring total IgE concentrations in bronchoalveolar lavage (BAL) samples obtained from intubated infants and by attempting to detect mRNA for IgE in cells obtained from both the upper and lower respiratory tract. Evidence of significant mast cell activation was sought by measuring tryptase concentrations in BAL fluid and serum. Detectable concentrations of IgE were found in two of seven BAL samples obtained more than five days after intubation and mRNA for IgE was demonstrated in three of six BAL samples and three of six samples obtained from the upper respiratory tract. Tryptase was detectable in 11 of 12 BAL samples with the two highest values detected on day 1. These values were raised compared with control samples but were not such to suggest that mast cell degranulation is the major contributor to the inflammatory process. These results suggest that IgE may be produced in the airways of infants in response to RSV infection. The relationships between IgE production, RSV infection, and symptoms of acute bronchiolitis remain obscure.
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PMID:Tryptase and IgE concentrations in the respiratory tract of infants with acute bronchiolitis. 771 46

During schistosomiasis, interleukin-5 (IL-5)-dependent eosinophil responses have been implicated in immunopathology, resistance to superinfection, synergistic interactions with chemotherapeutic agents, and the inductive phase of the egg-induced Th2 response. We examined these issues in IL-5-deficient (IL-5(-/-)) mice. IL-5(-/-) and wild-type (WT) mice were indistinguishable in terms of susceptibility to primary infections and the ability to resist secondary infections. Moreover, hepatic pathology was similar in both strains apart from a relative lack of eosinophils and, during chronic infection, a significantly larger mast cell component in the granulomas of IL-5(-/-) mice. Splenocyte cytokine production in response to soluble egg antigen (SEA) or anti-CD3 revealed no significant differences except for heightened tumor necrosis factor alpha production by cells from chronically infected IL-5(-/-) mice compared to WT animals. In contrast, ionomycin-stimulated non-B, non-T (NBNT) cells from IL-5(-/-) mice produced significantly smaller IL-4 amounts than did NBNT cells from WT animals. This difference was not apparent following plate-bound anti-immunoglobulin E or SEA stimulation. The absence of IL-5 failed to affect the induction of Th2 responses in naive mice. Peritoneal exudate cells recovered from egg-injected IL-5(-/-) or WT mice produced equivalent levels of IL-4 following restimulation with SEA or anti-CD3.
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PMID:Interleukin 5 (IL-5) is not required for expression of a Th2 response or host resistance mechanisms during murine schistosomiasis mansoni but does play a role in development of IL-4-producing non-T, non-B cells. 1033 13

Receptors that display negative signalling functions on lymphocytes and other cells of the reticuloendothelial system now number about 30. These negative receptors are transmembrane glycoproteins activated by phosphorylation of a tyrosine residue in immunoreceptor tyrosine-based inhibitory motifs that bind various phosphatases to induce dominant negative signals. Since these receptors are armed by the action of activating receptors and inhibit signalling by activating receptors, we have termed them coinhibitory receptors and the negative outcome is coinhibition. Coinhibitory receptors and some inhibitory mediators include FcgammaRIIB, CTLA-4, CD5, CD22, p58/70/140 KIR, gp49B1/gp91, PIRB1-5, LAIR-1, NKB1, Ly49 A/C/E/F/G, NKG2-A/B APC-R, CD66, CD72, PD-1, SHPS-1, SIRP-alpha1, ILT1-5, MIR7, 10, hMIR(HM18), hMIR(HM9), LIR1-3,5,8, Fas (CD95), TGFbeta-R, TNF-R1, IFNgamma-R (alpha and beta chains), mast cell function Ag, H2-M, HLA-DM, CD1, CD1-d, CD46, c-cbl, Pyk2/FADK2, P130 Ca rel prot, PGDF-R, LIF, LIF-R, CIS, SOCS13 and 5, and others are being defined regularly. This long list suggests that coinhibitors are needed not only for self-nonself discrimination, but also for control of ongoing responses to foreign antigens so that infectious agents are ideally dealt with by an appropriate level of immune responses to nonself and an appropriate amount of immunopathology and sickness behaviour.
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PMID:Why so many coinhibitory receptors? 1040 45

Asthma is a condition characterized by variable airflow obstruction, airway hyper-responsiveness (AHR) and airway inflammation which is usually, but not invariably, eosinophilic. Current thoughts on the pathogenesis of asthma are focused on the idea that it is caused by an inappropriate response of the specific immune system to harmless antigens, particularly allergens such as cat dander and house dust mite, that result in Th2-mediated chronic inflammation. However, the relationship between inflammation and asthma is complex, with no good correlation between the severity of inflammation, at least as measured by the number of eosinophils, and the severity of asthma. In addition, there are a number of conditions, such as eosinophilic bronchitis and allergic rhinitis, in which there is a Th2-mediated inflammatory response, but no asthma, as measured by variable airflow obstruction or AHR. Bronchoconstriction can also occur without obvious airway inflammation, and neutrophilic inflammation can in some cases be associated with asthma. When we compared the immunopathology of eosinophilic bronchitis and asthma, the only difference we observed was that, in asthma, the airway smooth muscle (ASM) was infiltrated by mast cells, suggesting that airway obstruction and AHR are due to an ASM mast cell myositis. This observation emphasizes that the features that characterize asthma, as opposed to bronchitis, are due to abnormalities in smooth muscle responsiveness, which could be intrinsic or acquired, and that inflammation is only relevant in that it leads to these abnormalities. It also emphasizes the importance of micro-localization as an organizing principle in physiological responses to airway inflammation. Thus, if inflammation is localized to the epithelium and lamina propria, then the symptoms of bronchitis (cough and mucus hypersecretion) result, and it is only if the ASM is involved -- for reasons that remain to be established -- that asthma occurs.
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PMID:New insights into the relationship between airway inflammation and asthma. 1214 12

The aim of the study was to investigate the effect of addition of montelukast to inhaled fluticasone propionate (FP) therapy, compared with FP therapy alone (100 microg twice a day) on airway immunopathology in individuals with mild asthma. Twenty-eight subjects received FP (100 microg twice a day) or FP (100 microg twice a day) plus montelukast (10 mg at night) for 8 weeks and were then crossed over to the alternate treatment for a further 8 weeks. Physiological measurements and bronchial biopsies were obtained at +/- 2 days before treatment and +/- 2 days at the end of each treatment period. A two-period crossover analysis was performed and the mean and SE were calculated. There was no significant difference in percent predicted FEV1 (p = 0.51) or PC20 mg/ml (p = 0.81) between the two treatment regimes after 8 weeks of therapy. There was no difference in the efficacy of either treatment in decreasing T cell (p = 0.97), CD45RO+ (p = 0.37), mast cell (p = 0.37), or activated eosinophils (p = 0.55) numbers in bronchial biopsies. There was no significant difference in the percentage area stained for IFN-gamma (p = 0.76) or interleukin-4 (p = 0.61) between treatments. Reduction of inflammatory cell numbers in the bronchial mucosa achieved with FP plus montelukast was not significantly different from the reduction observed with FP alone in individuals with mild asthma.
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PMID:Effect of the addition of montelukast to inhaled fluticasone propionate on airway inflammation. 1455 60


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