Tunon de Lara J M, Okayama Y, Savineau J P, Marthan R
Laboratoire de Physiologie, Université de Bordeaux II, France.
Eur Respir J. 1995 Nov;8(11):1861-5. doi: 10.1183/09031936.95.08111861.
Passive sensitization of human isolated lung with serum from atopic asthmatic patients provides an opportunity to study the link between airway hyper-responsiveness and the allergic process. To directly demonstrate the role of immunoglobulin E (IgE) in the effect of the atopic serum, we have compared the effect of passively sensitizing both human bronchi and isolated lung mast cells with either serum from atopic asthmatic patients or human monoclonal IgE. Peripheral bronchi ( < 5 mm in internal diameter) were dissected out from human lung obtained at thoractomy and isometric contraction was studied in response to a variety of immunological stimuli according to the sensitization protocol. Mast cells were also isolated from human lung and histamine release was measured under similar experimental conditions. A contractile response was elicited by either the specific antigen or anti-IgE (0.6-600 ng.mL-1) but not anti-immunoglobulin G (IgG) 0.2-20 micrograms.mL-1) in airways sensitized with atopic serum (total IgE concentration of approximately 1,000 international units (IU).mL-1). The maximal contractile response to anti-IgE was 75 +/- 22% of the response to 1 mM acetylcholine. Similarly, anti-IgE released histamine from isolated lung mast cells sensitized with atopic serum up to 22.4 +/- 2% of total histamine measured within mast cells. When isolated airways or mast cells were sensitized with human monoclonal IgE (1,000 IU.mL-1), response to anti-IgE in terms of contractile response or histamine release, respectively, were not significantly different from those obtained following passive sensitization with atopic serum. Finally, the bronchial contractile response to anti-IgE depended not only on the concentration of anti-IgE but also on that of IgE (300-2,000 IU.mL-1) used to sensitize the airways. These results indicate that the effect of antigen or anti-IgE in peripheral bronchi passively sensitized with atopic serum is mimicked when sensitization is carried out directly with human monoclonal IgE.
用特应性哮喘患者的血清对人离体肺进行被动致敏，为研究气道高反应性与过敏过程之间的联系提供了一个机会。为了直接证明免疫球蛋白E（IgE）在特应性血清作用中的作用，我们比较了用人特应性哮喘患者的血清或人单克隆IgE对人支气管和离体肺肥大细胞进行被动致敏的效果。从开胸手术获取的人肺中解剖出外周支气管（内径<5mm），并根据致敏方案研究其对各种免疫刺激的等长收缩反应。肥大细胞也从人肺中分离出来，并在类似的实验条件下测量组胺释放。在用特应性血清致敏的气道中（总IgE浓度约为1000国际单位（IU）/mL），特异性抗原或抗IgE（0.6 - 600ng/mL）可引发收缩反应，但抗免疫球蛋白G（IgG）（0.2 - 20μg/mL）则不能。抗IgE的最大收缩反应为对1mM乙酰胆碱反应的75±22%。同样，抗IgE可使用特应性血清致敏的离体肺肥大细胞释放组胺，释放量高达肥大细胞内总组胺量的22.4±2%。当用人类单克隆IgE（1000IU/mL）对离体气道或肥大细胞进行致敏时，抗IgE在收缩反应或组胺释放方面的反应与用特应性血清进行被动致敏后的反应无显著差异。最后，支气管对抗IgE的收缩反应不仅取决于抗IgE的浓度，还取决于用于致敏气道的IgE（300 - 2000IU/mL）的浓度。这些结果表明，当直接用人单克隆IgE进行致敏时，其在外周支气管中产生的效果与用特应性血清被动致敏后抗原或抗IgE产生的效果相似。
