Combined nasal challenge with diesel exhaust particles and allergen induces in vivo IgE isotype switching
Combined nasal challenge with diesel exhaust particles and allergen induces in vivo IgE isotype switching
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DOI：
10.1165/ajrcmb.19.3.3143
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发表时间：
1998-09-01
影响因子：
6.4
通讯作者：
Saxon, A
中科院分区：
文献类型：
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作者：
Fujieda, S;Diaz-Sanchez, D;Saxon, A
在这项研究中，我们致力于提供鼻腔感染后局部体内同型转换为IgE的证据，通过一种新的基于套式聚合酶链式反应的方法检测缺失的开关环DNA(开关环)作为Ig同型转换的确凿的分子证据。用柴油机尾气微粒(DEP)加豚草抗原对人进行鼻腔攻击，已被证明能促进局部IgE产生，刺激局部细胞因子产生，并显著增加粘膜抗豚草IgE抗体。在DEP加豚草联合激发4天后，我们从鼻腔灌洗细胞中检测并鉴定了缺失的开关环状DNA克隆(S epsilon/S m)，代表着从u到epsilon的转换。在单独用DEP或单独用豚草变应原攻击后，在鼻腔灌洗细胞中没有检测到开关环状DNA。这些结果表明，粘膜刺激与DEP和豚草变应原相结合，能够在体内驱动豚草过敏患者体内同型转换为IgE。这些结果首次直接证明了人类体内的IgE同型转换。
In this study we undertook to provide evidence for local in vivo isotype switching to IgE following nasal challenges, Detection of deleted switch circular DNA (switch circles) by a novel nested polymerase chain reaction-based approach was employed as definitive molecular evidence of Ig isotype switching. Nasal challenge in humans with diesel exhaust particles (DEP) plus ragweed antigen has been shown to enhance local IgE production, stimulate local cytokine production, and markedly increase mucosal IgE antibody to ragweed. Four days after combined intranasal DEP plus ragweed challenge, we detected and characterized clones of deleted switch circular DNA (S epsilon/S mu) representing switching from mu to epsilon from nasal lavage cells. No switch circular DNA was detected in nasal lavage cells following challenge with DEP alone nor with ragweed allergen alone. These results indicate that the combination of mucosal stimulation with DEP and ragweed allergen is capable of driving in vivo isotype switching to IgE in humans with ragweed allergy. These results are the first direct demonstration of in vivo IgE isotype switching in humans.