Oettgen H C, Martin T R, Wynshaw-Boris A, Deng C, Drazen J M, Leder P
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115.
Nature. 1994 Aug 4;370(6488):367-70. doi: 10.1038/370367a0.
The IgE-triggered release of mast cell mediators in response to antigen is thought to be the primary event in immediate hypersensitivity reactions such as systemic anaphylaxis. Although mast cells and basophils can be activated in vitro by non-IgE stimuli, it is not known whether these triggers lead to physiological changes in vivo. To investigate this possibility, we generated mice with a homozygous null mutation of the C epsilon gene. Such mice make no IgE, but produce other immunoglobulin isotypes normally. We report that despite the IgE deficiency, sensitized mutant mice become anaphylactic on antigen challenge and display tachycardia and pulmonary function changes similar to those seen in wild-type animals. These responses are accompanied by vascular leak, sharply elevated plasma histamine and rapid death. IgE-independent anaphylaxis does not depend on complement activation, but, as indicated in studies using genetically immunodeficient RAG-2- and SCID mice, does require a functional immune system. Such results clearly demonstrate that non-IgE pathways for hypersensitivity reactions exist in mice.
在诸如全身性过敏反应等速发型超敏反应中，免疫球蛋白E（IgE）触发肥大细胞介质对抗原作出反应而释放，被认为是主要事件。虽然肥大细胞和嗜碱性粒细胞在体外可被非IgE刺激激活，但尚不清楚这些触发因素是否会导致体内生理变化。为了研究这种可能性，我们培育出了携带Cε基因纯合无效突变的小鼠。这类小鼠不产生IgE，但能正常产生其他免疫球蛋白同种型。我们报告，尽管存在IgE缺陷，但致敏的突变小鼠在受到抗原攻击时会发生过敏反应，并表现出心动过速和肺功能变化，与野生型动物所见相似。这些反应伴有血管渗漏、血浆组胺急剧升高和迅速死亡。不依赖IgE的过敏反应不依赖补体激活，但如使用基因免疫缺陷的RAG-2和严重联合免疫缺陷（SCID）小鼠的研究所表明的，确实需要一个功能正常的免疫系统。这些结果清楚地表明，小鼠中存在超敏反应的非IgE途径。
