International archives of allergy and applied immunology最新文献

The sites and concentrations of Der p I within the house dust mite were determined. Highest concentrations were found in the epithelium of the posterior end of the mite stomach, implying that this is the site of Der p I synthesis and secretion.

Flexible fibre-optic bronchoscopy under local anaesthesia has been used to investigate the cellular airway events in atopic asthma. The findings have been compared to those from atopic individuals without asthma and non-atopic healthy controls, in an attempt to discern those changes relevant to clinical disease expression. Immunohistochemical and electron-microscopic analyses of airway biopsies identified that an atopic diathesis is associated with tissue eosinophil infiltration and mast cell degranulation. The eosinophilia was greatest in those atopic individuals with asthma. Flow-cytometric analysis of airway lavage revealed significantly enhanced T lymphocyte activation in clinical asthma. These findings are consistent with the hypothesis that T lymphocyte activation, through cytokine release, amplifies the tissue eosinophilia in asthma and that this combination is associated with clinical disease expression.

The prevalence of exercise-induced asthma (EIA) was determined in a population of 12- and 13-year-old schoolchildren whose parents returned a questionnaire regarding a previous diagnosis of asthma, recent asthmatic symptoms and symptoms of allergic rhinitis. EIA was defined as a greater than 15% fall in peak expiratory flow rate (PEFR) following 6 min of free running in a gymnasium. Among the 201 children studied, 18 (8.9%) demonstrated EIA. Of 21 children with symptomatic asthma in the 6 months prior to study, 9 (43%) developed EIA compared to none of 6 children with asymptomatic asthma (p less than 0.0001). Among 48 children with a history of allergic rhinitis alone, 7 (14.6%) demonstrated EIA. The mean postexercise changes in PEFR were 14.9% for 16 children with both asthma and allergic rhinitis, 6.4% among 48 children with allergic rhinitis only, and 1.8% among 125 normal children. Recent symptoms of asthma and a history of allergic rhinitis appeared to be risk factors for EIA. EIA was readily demonstrated in a gym class setting; the use of such screening may facilitate its diagnosis and treatment.

Dermal administration of either hydrocortisone or fluprednidene to healthy skin causes only a weak and short-lasting increase of the proportion of the anti-inflammatory macrophage RM 3/1 in the blood compared to the effect of the systemic application of glucocorticoids on this cell subtype. On the other hand, a rather permanent increase of these macrophages could be observed in untreated patients suffering from certain skin diseases, e.g. urticaria, atopic dermatitis, psoriasis.

We investigated the interactions of exogenous leukotriene A4 (LTA4) with isolated cells in the presence or absence of cellular stimuli. The majority of isolated cells are able to transform exogenous LTA4 into LTB4 as well as LTC4. In eosinophils, LTA4 induced 15-hydroxy-eicosatetranoic acid formation and was converted into LTB4. The Ca-ionophore-induced generation of LTB4 from polymorphonuclear leukocytes or from the cell fraction containing lymphocytes, monocytes and basophils was significantly suppressed with LTA4 while the formation of LTC4 was increased. Conversely, the Na-fluoride- and fMLP-induced generation of LTB4 was significantly increased. Our results suggest that the stimulus and the cellular composition determine the pattern of the generated inflammatory mediators.

A 41-kD component of Candida albicans was identified to be the major antigen radioimmunoprecipitated by antibodies with increased titers in the sera of patients with invasive candidiasis. A mouse monoclonal antibody (RJ5) was generated which, by immunoblotting, showed positive reactivity to the immunoprecipitated 41-kD component. By two-dimensional gel electrophoresis and immunoblotting, MoAb RJ5 was shown to react with different isoforms of the 41-kD component with pI values from 6.1 to 6.9. Furthermore, MoAb RJ5 showed positive reactivity to cytoplasmic antigens of C. albicans by frozen section and immunoperoxidase staining. By SDS-polyacrylamide gel electrophoresis and immunoblotting, MoAb RJ5 showed no cross-reactivity to antigens of Candida tropicalis and Candida parapsilosis. The epitope of the 41-kD molecule recognized by MoAb RJ5 was susceptible to treatment of proteinase K at concentrations of greater than or equal to 5 micrograms/ml, and was relatively resistant to periodate oxidation with concentration of NaIO4 up to 20 mM. This MoAb may be useful in the purification and characterization of the immunodominant 41-kD antigen of C. albicans, and as a probe in the detection of Candida antigens in the sera of patients with invasive candidiasis.

Endotoxin (lipopolysaccharide or LPS) inhalation has been implicated in increased pulmonary edema, most likely due to activation of an inflammatory response. The purpose of this study was to determine the cell types in the lung responsible for binding inhaled lipid A from Enterobacter agglomerans LPS. Five-hour exposures of aerosolized lipid A resulted in measurable pulmonary edema in hamsters, as determined by the accumulation of lung water. Immunocytochemistry was used to localize the inhaled lipid A in the cell types in the lung. Alveolar macrophages had decreased levels of lipid A as compared to unexposed controls, suggesting a possible metabolism by the macrophages. In vitro exposure of macrophages to lipid A resulted in a time-dependent clearance of lipid A which was inversely related to its concentration. Alveolar macrophages thus appear to be responsible for the removal of inhaled lipid A in this model and may initiate the physiological events which bring about pulmonary edema.

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin, frequently associated with a family history of atopy, raised serum IgE levels and other immunological abnormalities. Both eosinophils and their basic proteins have been detected in the skin lesions of AD patients. We measured the levels of eosinophil cationic protein (ECP) in sera of 24 children with AD and found them to be increased, compared to nonatopic controls, both children and adults. High ECP values were also obtained in 3 patients with the hyper-IgE syndrome. However, no direct relationship between IgE and ECP serum levels could be established. We found no correlation between serum ECP and the number of circulating eosinophils, suggesting that part of ECP was produced by cells infiltrating the tissues. Measurement of ECP might represent a noninvasive tool to assess the activity of AD in relation to eosinophil involvement in this disease.

The capacity of corticosteroids to inhibit the secretion of cytokines and the expression of selective antigens on monocytes has been studied in corticosteroid-sensitive (CS) and corticosteroid-resistant (CR) asthmatic patients. Incubation of monocytes derived from CS subjects with hydrocortisone inhibited the production of the enhancing activity, whereas in CR subjects hydrocortisone at concentrations of up to 10(-4) M did not suppress the release of enhancing activity. There was a rank order of potency for corticosteroid action: hydrocortisone less than methylprednisolone less than dexamethasone. The major activity was characterized as a heat-sensitive peptide of 3,000 daltons. The expression of CR1, CR3 and class II on asthmatic peripheral-blood mononuclear cells was increased relative to normal control donors. Culturing monocytes for 24 h in the presence of 10(-4) M hydrocortisone inhibited the expression of CR1, CR3 and class II in CS subjects but not in CR individuals. These results suggest that monocytes of CR asthmatic patients can increase the inflammatory potential of neutrophils and that they are hyperactive, as indicated by increased cytokine production and enhanced expression of activation markers, despite the presence of corticosteroids.

In atopic subjects, intradermal injection of platelet-activating factor (PAF), 40 and 400 ng, resulted in an immediate edema reaction markedly blocked by cetirizine, 10 mg twice a day. PAF challenge also induced a significant eosinophil accumulation evidenced by a skin window technique at 2, 4, 8 and 24 h. This inflammatory phenomenon was significantly inhibited by cetirizine. In patients with chronic urticaria, PAF, 100 micrograms intradermally, induced immediate and late cutaneous reactions (LCR) also blocked by cetirizine, 10 mg twice a day. These LCR were accompanied by an infiltration of the deep dermis by degranulated eosinophils. The pathophysiological mechanism of the PAF-induced skin reactions is discussed as well as the mechanism of action of cetirizine.