Does IgE bind to and activate eosinophils from patients with allergy?
(17/2860)
Human eosinophils have been reported to express both the mRNA and protein for the high affinity IgE receptor (FcepsilonRI); it is speculated that this receptor plays a role in eosinophil mediator release in allergic diseases. However, questions still remain. How much of the FcepsilonRI protein is actually expressed on the cell surface of the eosinophil? If they are present, are these IgE receptors associated with effector functions of eosinophils? To address these issues, we studied blood eosinophils from patients with ragweed hay fever. A high level of low affinity IgG receptor (FcgammaRII, CD32), but no expression of FcepsilonRI, was detectable on the eosinophil surface by standard FACS analysis. However, after in vitro sensitization with biotinylated chimeric IgE (cIgE), cell-bound cIgE was detected by PE-conjugated streptavidin. This cIgE binding was partially inhibited by anti-FcepsilonRI mAb, suggesting that eosinophils do express minimal amounts of FcepsilonRI detectable only by a sensitive method. Indeed, FACS analysis of whole blood showed that eosinophils express approximately 0.5% of the FcepsilonRI that basophils express. When stimulated with human IgE or anti-human IgE, these eosinophils did not exert effector functions; there was neither production of leukotriene C4 or superoxide anion nor any detectable degranulation response. In contrast, eosinophils possessed membrane-bound human IgG and showed functional responses when stimulated with human IgG or anti-human IgG. Thus, IgG and/or cytokines, such as IL-5, appear to be more important for eosinophil activation in allergic diseases than IgE. (+info)
Development of a flow cytometry assay for the identification and differentiation of chemicals with the potential to elicit irritation, IgE-mediated, or T cell-mediated hypersensitivity responses.
(18/2860)
These studies were conducted to investigate the potential use of a flow cytometric analysis method for the identification and differentiation of chemicals with the capacity to induce irritation, IgE- or T cell-mediated hypersensitivity responses. An initial study investigated the ability of equally sensitizing concentrations (determined by local lymph node assay) of IgE-mediated (Toluene Diisocyanate-TDI) and T cell-mediated (Dinitrofluorobenzene-DNFB) allergens to differentially modulate the IgE+B220+ population in the lymph nodes draining the dermal exposure site. Sodium lauryl sulfate (SLS) was also tested as a nonsensitizing irritant control. Female B6C3F1 mice were dermally exposed once daily for 4 consecutive days, with the optimum time point for analysis determined by examining the IgE+B220+ population 8, 10, and 12 days post-initial chemical exposure. At the peak time point, day 10, the IgE+B220+ population was significantly elevated in TDI (41%), while moderately elevated in DNFB (18%) exposed animals when compared to the vehicle (0.8%), and remained unchanged in SLS (2.2%) exposed animals when compared to the ethanol control (2.5%). Experiments in our laboratory and others have demonstrated that the draining lymph node B220+ population becomes significantly elevated following exposure to allergens (IgE- and T cell-mediated), not irritants, allowing for their differentiation. An existing mouse ear swelling assay was used to identify chemical irritants. Therefore, using the endpoints of percent ear swelling, percent B220+ cells, and percent IgE+B220+ cells, a combined irritancy/phenotypic analysis assay was developed and tested with tetradecane (irritant), toluene diisocyanate, trimellitic anhydride (IgE-mediated allergens), benzalkonium chloride, dinitrofluorobenzene, oxazolone, and dinitrochlorobenzene (T cell-mediated allergens) over a range of concentrations. Based upon the pattern of response observed, a paradigm was developed for continued evaluation: Irritant exposure will result in significant ear swelling without altering the B220+ or IgE+B220+ populations. Exposure to sensitizers (IgE-mediated or T cell-mediated) will increase the B220+ population and the percent ear swelling will remain unchanged or will significantly increase, depending on the irritancy capacity of the chemical. Both the IgE+B220+ and B220+ populations will become elevated at the same test concentration following exposure to IgE-mediated, hypersensitivity inducing allergens. At its peak, the percent of IgE+B220+ cells will be equal to the percent of B220+ cells. The B220+ population will increase at a lower test concentration than the IgE+B220+ population, following exposure to T cell-mediated, hypersensitivity inducing allergens. At its peak, the percent of IgE+B220+ cells will reach less than half that of the percent of B220+ cells. The irritancy/phenotypic analysis method may represent a single murine assay able to identify and differentiate chemicals with the capacity to induce irritation, or IgE-mediated or T cell-mediated responses. (+info)
Establishment of antigen-specific IgE transgenic mice to study pathological and immunobiological roles of IgE in vivo.
(19/2860)
We have established transgenic mice that carry the genes coding for heavy and light chains of TNP-specific IgE. They produced high titers of TNP-specific IgE (20-40 microg/ml in serum) and their mast cells were heavily loaded with IgE. The level of FcepsilonRI expression on their mast cells was 6-8 times higher than that in non-transgenic littermates. The expression of low-affinity IgE receptor FcepsilonRII (CD23) on splenic B cells was also 6-8 times higher in the transgenic mice. Consistent with this, substantial amounts of IgE were detected on B cells in the transgenic mice. When challenged with i.v. administration of the corresponding antigen, the transgenic mice exhibited systemic anaphylactic symptoms such as a drastic drop of body temperature and extravasation of administered dye. Biphasic (immediate and delayed) ear swelling response was also elicited in a TNP-specific manner by epicutaneous antigen challenge without any prior sensitization. Thus, IgE produced in the transgenic mice was found to be biologically active to induce both local and systemic allergic reactions in vivo upon the challenge of the corresponding antigen. Taken together, the antigen-specific IgE transgenic mice established for the first time in this study appear to provide an attractive model system to study the pathological roles of IgE in acute and chronic phases of allergic inflammation as well as their immunobiological roles in vivo. They may also be useful to develop novel therapeutic strategies for atopic disorders. (+info)
Shifts in lung lymphocyte profiles correlate with the sequential development of acute allergic and chronic tolerant stages in a murine asthma model.
(20/2860)
T lymphocytes have a central regulatory role in the pathogenesis of asthma. We delineated the participation of lymphocytes in the acute allergic and chronic tolerant stages of a murine model of asthma by characterizing the various subsets of lymphocytes in bronchoalveolar lavage and lung tissue associated with these responses. Acute (10-day) aerosol challenge of immunized C57BL/6J mice with ovalbumin resulted in airway eosinophilia, histological evidence of peribronchial and perivascular airway inflammation, clusters of B cells and TCRgammadelta cells in lung tissue, increased serum IgE levels, and airway hyperresponsiveness to methacholine. In mice subjected to chronic (6-week) aerosol challenge with ovalbumin, airway inflammation and serum IgE levels were significantly attenuated and airway hyperresponsiveness was absent. The marked increases in lung B and T cell populations seen in the acute stage were also significantly reduced in the chronic stage of this model. Thus, acute ovalbumin challenge resulted in airway sensitization characteristic of asthma, whereas chronic ovalbumin challenge elicited a suppressed or tolerant state. The transition from antigenic sensitization to tolerance was accompanied by shifts in lymphocyte profiles in the lung and bronchoalveolar lavage fluid. (+info)
Occupational allergies and asthma.
(21/2860)
OBJECTIVE: To review aspects of occupational allergies and asthma for primary care physicians recognizing, diagnosing, and managing patients with these conditions. QUALITY OF EVIDENCE: Studies in the medical literature mainly provide level 2 evidence, that is, from at least one well-designed clinical trial without randomization, from cohort or case-control analytical studies, from multiple time series, or from dramatic results in uncontrolled experiments. MAIN MESSAGE: Occupational allergies and asthma have the best prognosis with an early, accurate diagnosis and subsequent avoidance of exposure to the relevant sensitizer. These diagnoses can normally be suspected from the clinical history. Primary care physicians can also initiate investigations to make an objective diagnosis, can assess workplace exposure agents from the history, and can review appropriate data sheets on material safety. Specialist evaluation is likely to be needed for skin tests, however, and for other specialized tests (such as pulmonary function assessments at work and off work or specific challenges with the suspected workplace agent). Patients with a confirmed diagnosis need appropriate medical management of their allergic manifestations or asthma, but also often require psychosocial support during the period of investigation and management, especially in relation to required changes in their work and to compensation or insurance claims. CONCLUSIONS: Consider workplace exposure as a source of patients' allergies or asthma and aim to make an early, accurate diagnosis. (+info)
Thiazolidinedione inhibits production of RANTES in a cytokine-treated human lung epithelial cell line.
(22/2860)
The chemokine RANTES is a potent chemoattractant for eosinophils. RANTES is produced by lung epithelial cells during eosinophil-rich inflammatory diseases such as asthma. In this study, we examined the effects of thiazolidinediones (TZD) on RANTES expression in a human lung epithelial cell line, A549. In A549 cells, interleukin-1beta and tumor necrosis factor-alpha induced endogenous RANTES protein secretion, mRNA expression, and promoter activity. The TZD inhibited these effects. Our data indicate that the suppression of the expression of RANTES can be accomplished by TZD treatment, raising the possibility that TZD might be of therapeutic value in diseases such as asthma. (+info)
The influence of chronic yogurt consumption on immunity.
(23/2860)
There has been increased interest in the study of nutrition and immunity. This is especially true with respect to the hypothesis that consumption of specific foods may reduce an individual's susceptibility to the establishment and/or progression of immunologic disease. Although an increased intake of a specific food may improve health status in select cases, chronic consumption of large amounts of one specific food may in fact be detrimental. The studies described here examined the long-term effect of yogurt consumption on two different age populations, young adults (20-40 y) and senior adults (55-70 y). There were three study groups per age group, live-culture yogurt, pasteurized yogurt and control (no yogurt), given 200 g/d of yogurt for 1 y. The subjects completed a questionnaire detailing health parameters on a weekly basis and a 4-d food record was taken monthly. Blood was taken every 3 mo and complete blood chemistry, blood count, total and specific immunoglobulin (Ig)E, and interferon-gamma (IFN-gamma) production measured. Yogurt consumption, especially for the live-culture groups, was associated with a decrease in allergic symptoms in both age groups. Seniors in the control group experienced an increase in both total and LDL cholesterol, whereas those in the yogurt groups remained stable during the course of the study. There was little effect on IFN-gamma and IgE production, although seniors in the yogurt group had lower levels of total IgE throughout the year. (+info)
Prevalence of allergic sensitization to regional inhalants among allergic patients in Jakarta, Indonesia.
(24/2860)
Sensitization towards a panel of eight regional inhalant allergens was evaluated among 107 patients with allergic rhinitis and/or asthma. A total of 32 children (age 5-13 years, mean 9 years; 18 male, 14 female), 75 adolescents and adults (aged 14-66 years, mean 32 years; 21 male, 54 female) and 20 normal control volunteers (aged 16-46, mean 30 years; 4 male, 16 female) were evaluated via skin prick test. A weal response of 3 x 3 mm or greater was taken to be positive. The sensitization rates among individuals to these allergens were: house dust mites, Dermatophagoides pteronyssinus (77.57%), Blomia tropicalis (71.96%), Austroglycyphagus malaysiensis (33.64%), pollen, palm oil Elaeis guineensis (22.43%), Acacia auriculiformis (12.15%), fern spore, resam Dicranopteris spp (11.21%), fungal spores: Curvularia fallax (8.41%) and Exserohilum rostratum (13.08%). There were significantly higher frequencies of sensitization to these allergens among allergic individuals compared to normal controls, and among atopic individuals with two allergy manifestations (rhinitis and asthma) compared to those with only one. No difference was noted between children and adults in the allergic group. In conclusion, the allergic patients were highly sensitized to dust mites and sensitization to regional pollen and spores was also documented. They should be considered as relevant and be included in skin test batteries in Indonesia. (+info)