Yamaguchi M, Lantz C S, Oettgen H C, Katona I M, Fleming T, Miyajima I, Kinet J P, Galli S J
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
J Exp Med. 1997 Feb 17;185(4):663-72. doi: 10.1084/jem.185.4.663.
The binding of immunoglobulin E (IgE) to high affinity IgE receptors (Fc(epsilon)RI) expressed on the surface of mast cells primes these cells to secrete, upon subsequent exposure to specific antigen, a panel of proinflammatory mediators, which includes cytokines that can also have immunoregulatory activities. This IgE- and antigen-specific mast cell activation and mediator production is thought to be critical to the pathogenesis of allergic disorders, such as anaphylaxis and asthma, and also contributes to host defense against parasites. We now report that exposure to IgE results in a striking (up to 32-fold) upregulation of surface expression of Fc(epsilon)RI on mouse mast cells in vitro or in vivo. Moreover, baseline levels of Fc(epsilon)RI expression on peritoneal mast cells from genetically IgE-deficient (IgE -/-) mice are dramatically reduced (by approximately 83%) compared with those on cells from the corresponding normal mice. In vitro studies indicate that the IgE-dependent upregulation of mouse mast cell Fc(epsilon)RI expression has two components: an early cycloheximide-insensitive phase, followed by a later and more sustained component that is highly sensitive to inhibition by cycloheximide. In turn, IgE-dependent upregulation of Fc(epsilon)RI expression significantly enhances the ability of mouse mast cells to release serotonin, interleukin-6 (IL-6), and IL-4 in response to challenge with IgE and specific antigen. The demonstration that IgE-dependent enhancement of mast cell Fc(epsilon)RI expression permits mast cells to respond to antigen challenge with increased production of proinflammatory and immunoregulatory mediators provides new insights into both the pathogenesis of allergic diseases and the regulation of protective host responses to parasites.
免疫球蛋白E（IgE）与肥大细胞表面表达的高亲和力IgE受体（Fc(ε)RI）结合，使这些细胞在随后接触特定抗原时被激活并分泌一组促炎介质，其中包括一些也具有免疫调节活性的细胞因子。这种IgE和抗原特异性的肥大细胞激活及介质产生被认为在过敏性疾病（如过敏反应和哮喘）的发病机制中起关键作用，同时也有助于宿主抵抗寄生虫。我们现在报告，在体外或体内，接触IgE会导致小鼠肥大细胞表面Fc(ε)RI的表达显著上调（高达32倍）。此外，与相应正常小鼠的细胞相比，基因敲除IgE（IgE -/-）小鼠腹膜肥大细胞上Fc(ε)RI的基础表达水平显著降低（约83%）。体外研究表明，IgE依赖的小鼠肥大细胞Fc(ε)RI表达上调有两个阶段：一个早期对放线菌酮不敏感的阶段，随后是一个对放线菌酮抑制高度敏感的后期且更持久的阶段。反过来，Fc(ε)RI表达的IgE依赖性上调显著增强了小鼠肥大细胞在受到IgE和特异性抗原刺激时释放5-羟色胺、白细胞介素-6（IL-6）和IL-4的能力。IgE依赖性增强肥大细胞Fc(ε)RI表达使肥大细胞能够对抗原刺激产生更多促炎和免疫调节介质，这一发现为过敏性疾病的发病机制以及宿主对寄生虫的保护性反应调节提供了新的见解。
