Rabe K F, Watson N, Dent G, Morton B E, Wagner K, Magnussen H, Heusser C H
Krankenhaus Grosshansdorf, Zentrum für Pneumologie und Thoraxchirurgie, LVA Hamburg, Germany.
Am J Respir Crit Care Med. 1998 May;157(5 Pt 1):1429-35. doi: 10.1164/ajrccm.157.5.9708127.
We investigated the effect of a novel mouse IgG2b nonanaphylactogenic anti-human IgE antibody, 17-9, on allergen and histamine responses in passively sensitized human airways in vitro to determine the specific contribution of IgE to the sensitization process. Bronchial rings were sensitized with serum containing high levels of allergen-specific IgE (Dermatophagoides farinae), or with a hapten-specific chimeric humanized IgE (JW8). There was a concentration-dependent contraction of serum-sensitized bronchial rings to D. farinae (517 +/- 188 mg tension at 10 U/ml, n = 8) that was not observed in nonsensitized controls. This response was practically abolished when tissues were sensitized in the presence of 100 microg/ml anti-IgE antibody 17-9 (54 +/- 20 mg). In tissues sensitized with the anti-NIP IgE, JW8, there was a concentration-dependent contraction to the specific antigen NIP-BSA (560 +/- 154 mg at 0.3 microg/ml, n = 5) that was not observed in nonsensitized control subjects and that was substantially inhibited when 17-9 was present in the sensitization buffer (124 +/- 109 mg). The inhibition with 17-9 was specific, as pretreatment with a non-IgE-specific IgG2b antibody did not affect allergen responses. Potency and maximal contractions to histamine in serum-sensitized tissues were significantly elevated compared with nonsensitized controls; this was not affected by the presence of 17-9 during sensitization (pEC50 = 5.1 +/- 0.2 versus 5.0 +/- 0.3 in tissues sensitized in the absence of 17-9). In tissues sensitized with JW8 there was no significant increase in responsiveness to histamine. We conclude that allergen responses in sensitized human airways are dependent on IgE levels in the sensitizing serum while nonspecific (hyper)responsiveness depends on serum factors other than IgE. Nonanaphylactogenic anti-human IgE antibodies effectively inhibit allergen responses of human airways in vitro but may not affect other factors inducing hyperresponsiveness.
我们研究了一种新型小鼠IgG2b非过敏性抗人IgE抗体17 - 9对体外被动致敏的人呼吸道中变应原和组胺反应的影响，以确定IgE在致敏过程中的具体作用。用含有高水平变应原特异性IgE（粉尘螨）的血清或半抗原特异性嵌合人源化IgE（JW8）对支气管环进行致敏。血清致敏的支气管环对粉尘螨有浓度依赖性收缩（10 U/ml时张力为517±188 mg，n = 8），未致敏的对照中未观察到这种情况。当组织在100μg/ml抗IgE抗体17 - 9存在下致敏时，这种反应几乎完全消除（54±20 mg）。在用抗NIP IgE（JW8）致敏的组织中，对特异性抗原NIP - BSA有浓度依赖性收缩（0.3μg/ml时为560±154 mg，n = 5），未致敏的对照受试者中未观察到这种情况，且当致敏缓冲液中存在17 - 9时，收缩显著受到抑制（124±109 mg）。17 - 9的抑制作用具有特异性，因为用非IgE特异性IgG2b抗体预处理不影响变应原反应。与未致敏对照相比，血清致敏组织中对组胺的效价和最大收缩显著升高；致敏过程中17 - 9的存在对此无影响（无17 - 9致敏的组织中pEC50 = 5.1±0.2，有17 - 9致敏的组织中pEC50 = 5.0±0.3）。在用JW8致敏的组织中，对组胺的反应性没有显著增加。我们得出结论，致敏的人呼吸道中的变应原反应取决于致敏血清中的IgE水平，而非特异性（高）反应性取决于IgE以外的血清因子。非过敏性抗人IgE抗体在体外有效抑制人呼吸道的变应原反应，但可能不影响诱导高反应性的其他因素。
