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  • 2000-2004  (2)
  • 2002  (2)
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  • 2000-2004  (2)
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  • 1
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Previous studies have shown that rat peritoneal mast cells and mast cell model rat basophilic leukaemia (RBL-2H3) cells generate intracellular reactive oxygen species (ROS) in response to antigen challenge. However, the physiological significance of the burst of ROS is poorly understood.Objective The present study was undertaken to investigate the role of superoxide anion in mediator release in rat and human cell systems.Methods RBL-2H3 cells were directly stimulated with anti-rat FcεRI α-subunit monoclonal antibody (mAb). For the analysis of human cell system, leucocytes were isolated by dextran sedimentation from healthy volunteers or from patients, and challenged either with anti-human FcεRI mAb or with the relevant antigens. Superoxide generation was determined by chemiluminescence-based methods. The releases of histamine and leukotrienes (LT)s were determined by enzyme-linked immunosorben assay (ELISA).Results Cross-linking of FcεRI on RBL-2H3 cells or on human leucocytes from healthy donors by the anti-FcεRI mAb resulted in a rapid generation of superoxide anion, as determined by chemiluminescence using superoxide-specific probes. Similarly, leucocytes from patients generated superoxide anion in response to the challenge with the relevant allergen but not with the irrelevant allergen. Furthermore, diphenyleneiodonium (DPI), a well-known inhibitor of flavoenzymes suppressed the superoxide generation and the release of histamine and LTC4 induced by the anti-FcεRI mAb or by allergen in parallel.Conclusion These results indicate that both RBL-2H3 cells and human basophils generate superoxide anion upon FcεRI cross-linking either by antibody or by allergen challenge and that blockade of the generation prevents the release of allergic mediators. The findings strongly support the role of superoxide generation in the activation of mast cells and basophils under both physiological and pathological conditions. The findings suggest that drugs regulating the superoxide generation have potential therapeutic use for allergic disorders.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Background  Annular erythema (AE) in Sjögren's syndrome (SS) usually develops on areas of sun-exposed skin and is exacerbated during summer. Objectives  To evaluate photosensitivity in SS and to investigate the involvement of ultraviolet (UV) radiation in the development of AE in SS. Methods  Phototesting with UVA and UVB was performed on 14 SS patients, including 10 with primary SS. Clinical and histological features as well as expression of inducible nitric oxide synthase (iNOS) in the evoked skin lesions were compared with those of lupus erythematosus (LE). Eleven SS patients had a history of photosensitive AE ( n  = 4), papules ( n  = 3) or other types ( n  = 4) of lesions on their sun-exposed skin that were induced or aggravated by sunlight exposure. Results  Phototesting induced a prolonged erythematous response ( n  = 8), infiltrated erythema (IE) ( n  = 4) and/or papules ( n  = 3) in 11 of 14 SS patients, including one with primary SS without a history of photosensitivity. Histologically, the induced IE and papules showed coat-sleeve-like or sparse perivascular infiltration of lymphocytes similar to that in primary skin lesions of AE in SS. No epidermal changes characteristic for LE were found except for partial and mild liquefaction degeneration in three cases. In contrast, two cases were indistinguishable from the papular type of polymorphic light eruption in several aspects, including their primary skin lesions and early response to a photoprovocation test. Immunohistochemistry revealed diffuse expression of iNOS throughout the epidermis, which is characteristic for LE, in the three SS patients with minimal liquefaction degeneration, while the remaining seven SS patients examined exhibited no iNOS staining or a normal expression pattern. Conclusions  Our results indicate that photosensitivity exists in certain primary SS patients, and that UV is critical to the development of AE in SS, probably through a pathological mechanism distinct from that in LE.
    Type of Medium: Electronic Resource
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