title: Airway exposure to bacterial superantigen (SEB) induces lymphocyte-dependent airway inflammation associated with increased airway responsiveness--a model for non-allergic asthma.
abstract: Although immunological consequences of systemic superantigen administration have been extensively studied, the effects of local mucosal exposure to superantigens are not well defined. The purpose of this study was to delineate the type of immune response triggered by superantigen exposure to the airway mucosa in mice. In dose-response experiments we determined a low dose of staphylococcal enterotoxin B (SEB) that triggered an inflammatory response characterized by mucosal and airway recruitment of lymphocytes, eosinophils and neutrophils together with elevated levels of IL-4, but not IFN-gamma, in bronchoalveolar lavage (BAL) fluids. TCR Vbeta analysis revealed that superantigen-responsive and -non-responsive T cells were equally recruited into the airways. SEB markedly enhanced the frequency of TNF-alpha-positive BAL macrophages as well as the amount of TNF-alpha in BAL fluids. These responses were associated with the development of increased airway responsiveness (AR) in SEB-treated mice. This effect occurred in an antibody-independent fashion. Furthermore, this type of response was observed in IgE-high responder BALB/c as well as in IgE-low/intermediate responder C57BL/6 mice. The development of increased AR was CD4+ T cell dependent as shown by transfer experiments into BALB/c nu/nu mice. These results suggest that the local immune response following mucosal superantigen administration triggers a unique inflammatory response in the airways resembling many features of "intrinsic asthma".
authors: Department of Laboratory Medicine and Pathobiochemistry, Charité, Campus Virchow-Clinic, Berlin, Germany.
authors: U
authors: U
authors: Herz
authors: R
authors: R
authors: Rückert
authors: K
authors: K
authors: Wollenhaupt
authors: T
authors: T
authors: Tschernig
authors: U
authors: U
authors: Neuhaus-Steinmetz
authors: R
authors: R
authors: Pabst
authors: H
authors: H
authors: Renz
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000008:administration & dosage / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D004768:Enterotoxins; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; C031818:enterotoxin B, staphylococcal