Imani F, Proud D, Griffin D E
Division of Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Asthma and Allergy Center, Baltimore, MD 21224,
J Immunol. 1999 Feb 1;162(3):1597-602.
Increasing evidence suggests that viral infections are associated with the induction and exacerbation of asthma. One characteristic of human asthma is an increase in the levels of circulating IgE. Previous studies have shown that circulating IgE levels are elevated during the early phase of infection with measles virus (MV). We have shown previously that one mechanism by which viral infections can increase IgE levels is via an induction of IgE class switching through the activation of the antiviral protein kinase (dsRNA-activated protein kinase), leading to the activation of multiple NF-kappaB complexes. Therefore, to determine whether infection with MV can also induce IgE class switching, we infected the human Ramos B cell line with the Edmonston strain of MV. Infecting Ramos cells with MV did not result directly in either the activation of dsRNA-activated protein kinase or IgE class switching. However, a synergistic effect on IgE class switching was observed when Ramos cells were infected with MV before IL-4 treatment. Ab cross-linking of the MV receptor, CD46, mimicked the effects of MV infection in synergizing with IL-4 to induce IgE class switching, suggesting that viral hemagglutinin is involved in this synergistic effect. These data provide the first indication of a potential mechanism for MV-induced IgE up-regulation and suggest a model for a viral-induced exacerbation of IgE-mediated disorders such as asthma.
越来越多的证据表明,病毒感染与哮喘的诱发和加重有关。人类哮喘的一个特征是循环IgE水平升高。先前的研究表明,在麻疹病毒(MV)感染的早期阶段,循环IgE水平会升高。我们之前已经表明,病毒感染增加IgE水平的一种机制是通过激活抗病毒蛋白激酶(dsRNA激活的蛋白激酶)诱导IgE类别转换,从而导致多种NF-κB复合物的激活。因此,为了确定MV感染是否也能诱导IgE类别转换,我们用MV的埃德蒙斯顿株感染了人Ramos B细胞系。用MV感染Ramos细胞并没有直接导致dsRNA激活的蛋白激酶的激活或IgE类别转换。然而,当Ramos细胞在IL-4处理前用MV感染时,观察到对IgE类别转换有协同作用。MV受体CD46的抗体交联模拟了MV感染与IL-4协同诱导IgE类别转换的作用,表明病毒血凝素参与了这种协同作用。这些数据首次表明了MV诱导IgE上调的潜在机制,并提出了病毒诱导IgE介导的疾病(如哮喘)加重的模型。