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  • 2000-2004  (4)
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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 32 (2002), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background The mechanisms involved in eosinophil recruitment by cysteinyl-leukotrienes (CysLTs) remain to be defined.Objective We investigated whether CysLTs LTC4, LTD4 and LTE4 could directly stimulate in vitro adhesion molecule expression and cell locomotion of blood eosinophils from atopic asthmatic donors. Methods Mab staining and FACS analysis were used to evaluate Mac-1 and LFA-1 expression on eosinophils before and after CysLTs stimulation. Eosinophil locomotion was tested using a 48-well Boyden microchamber. Results CysLTs, at the concentrations of 1 and 10 nM, were able to significantly up-regulate Mac-1 expression (P 〈 0.05, each comparison) but not LFA-1 expression (P 〉 0.05, each comparison). A dose-dependent, eosinophil chemotaxis was also induced by LTC4, LTD4 and LTE4 (0.1–10 nM) (P 〈 0.01, each comparison). Montelukast (0.01 nM to 10 nM), a specific CysLT1 receptor antagonist, significantly down-regulated LTC4, LTD4 and LTE4-induced Mac-1 expression (P 〈 0.01, each comparison) and the CysLT-induced eosinophil migration (P 〈 0.01, each comparison). In contrast, montelukast did not affect Mac-1 expression or cell migration when eosinophils were stimulated by the ‘non-specific activators’, such as fMLP or C5a (P 〉 0.05, each comparison).Conclusion These data demonstrate that CysLTs are active in vitro in directly up-regulating human eosinophil functions involved in eosinophil recruitment. The down-regulation of Mac-1 expression and eosinophil chemotaxis by the potent and selective CysLT1 receptor antagonist montelukast indicated the specificity of the LTC4-, LTD4- and LTE4-induced response.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 31 (2001), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In the asthmatic lung the altered expression of costimulatory molecules (CD80, CD86) by alveolar macrophages contributes to T lymphocyte activation and expansion. We hypothesized that CD80 and CD86 on alveolar macrophages could differentially support allergic inflammation in adult asthma. Here we studied 11 subjects with mild allergic asthma and 11 atopic non-asthmatics as controls. Dermatophagoides-specific T cell lines were derived from peripheral blood from each subject. Bronchoalveolar lavage with evaluation of lung inflammatory cells was performed in all individuals at baseline and 24 h after allergen challenge. The expression of CD80 and CD86 costimulatory molecules by alveolar macrophages was studied and, in parallel, the efficiency of antigen presentation was measured in terms of IL-4 and IL-5 production by allergen-stimulated autologous T cells. We found that in asthmatic subjects (i) the percent of CD80+, but not CD86+ alveolar macrophages was increased at baseline and did not change following allergen challenge; (ii) CD86, but not CD80, membrane expression was up-regulated following allergen challenge; (iii) both CD80 and CD86 were required to support Th2 cytokine production by allergen-specific T cells, with a prevalent role of CD86 after allergen challenge. Our data indicate that alveolar macrophages deliver costimulatory signals via CD80 and CD86, which support the production of Th2 cytokines by allergen-specific T cells. They also indicate that CD86 in vivo is up-regulated in the 24 h following allergen exposure and that this modulation is functionally relevant.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: In atopic individuals, exposure to allergens is followed by recruitment of blood eosinophils in the target tissue. We investigated whether allergen inhalation challenge could result in depletion of blood eosinophils overexpressing adhesion molecules involved in eosinophil migration.Methods: Blood eosinophils were isolated from seven atopic asthmatic patients and seven control subjects and the “at baseline” expression of lymphocyte function-associated antigen-1 (LFA-1), macrophage antigen-1 (Mac-1) and very late antigen-4 (VLA-4) was assessed by monoclonal antibody staining and flow cytometry analysis. Asthmatic patients underwent allergen challenge and the expression of LFA-1, Mac-1 and VLA-4 by blood eosinophils was again evaluated 3 h and 24 h after allergen challenge.Results: As compared to controls, eosinophils from atopics showed at baseline enhanced LFA-1 expression (P=0.0012), but similar Mac-1 or VLA-4 expression (P 〉 0.1, each comparison). In atopics, the percentage and absolute number of blood eosinophils were significantly decreased 3 h after allergen challenge (P=0.001 and P=0.022, respectively) but returned to similar values to prechallenge values after an additional 21 h (P 〉 0.1). Allergen challenge was also followed by a significant decrease in LFA-1 expression by eosinophils, at 3 h (P=0.002) and at 24 h (P=0.038), while no changes in Mac-1 and VLA-4 were observed. A significant correlation between postchallenge decrease in LFA-1 expression and in blood eosinophilia, both expressed as percentage (r=0.88; P 〈 0.01) or absolute number (r=0.87; P 〈 0.01) was demonstrated at 3 h (r=0.88; P 〈 0.01) but not at 24 h (r=0.64, P 〉 0.05 and r=0.11; P 〉 0.05, respectively).Conclusion: In allergic asthma, an early recruitment of blood eosinophils overexpressing LFA-1 occurs in the first hours after allergen challenge.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: In atopic subjects, dysfunctions of the upper and lower airways frequently coexist and allergic rhinitis seems to constitute a risk factor for the occurrence of asthma in predisposed individuals.Aim of the study: To evaluate whether in atopic subjects nasal inflammation could reflect changes in respiratory functions, 11 allergic children, sensitized to house dust mites (HDM), with rhinoconjunctivitis and asthma and 10 nonatopic controls (ctrs) were studied.Methods: All subjects underwent nasal brushing to detect percentages of nasal eosinophils (Eos %) and intercellular adhesion molecule-1 (ICAM-1) expression by nasal epithelial cells. In the same day pulmonary function tests, i.e. forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flows at 25–75% of the vital capacity (FEF25−75%) and methacholine (MCh) bronchial inhalation challenge were also evaluated.Results: Pulmonary function parameters were not significantly different in allergic children and in ctrs (P 〉 0.05), while a significant increase in bronchial reactivity to MCh, expressed as Pd20 MCh, was detected in the former population (P 〈 0.05). As compared with ctrs, allergic children showed elevated Eos % and ICAM-1 expression (P 〈 0.05). When nasal inflammation and pulmonary function parameters were compared, a significant correlation was found between nasal Eos % and bronchial reactivity to MCh (P = 0.002).Conclusions: These data support the concept of significant links between upper and lower respiratory tract involvement in atopic children sensitized to HDM.
    Type of Medium: Electronic Resource
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