Diaz-Sanchez D, Garcia M P, Wang M, Jyrala M, Saxon A
Hart and Louise Lyon Laboratory, Division of Clinical Immunology/Allergy, Department of Medicine, UCLA School of Medicine, University of California, Los Angeles, CA 90095-1680, USA.
J Allergy Clin Immunol. 1999 Dec;104(6):1183-8. doi: 10.1016/s0091-6749(99)70011-4.
Diesel exhaust particles (DEPs) increase in vivo IgE and cytokine production at the human upper respiratory mucosa, exacerbating allergic inflammation.
We examined the ability of DEP exposure to lead to primary sensitization of humans by driving a de novo mucosal IgE response to a neoantigen, keyhole limpet hemocyanin (KLH).
Ten atopic subjects were given an initial nasal immunization with 1 mg of KLH followed by 2 biweekly nasal challenges with 100 microg of KLH. Identical nasal KLH immunization was then performed on 15 different atopic subjects, but DEPs were administered 24 hours before each KLH exposure.
Exposure to KLH alone led to the generation of an anti-KLH IgG and IgA humoral response, which was detected in nasal fluid samples. No anti-KLH IgE appeared in any subjects. In contrast, when challenged with KLH preceded by DEPs, 9 of the 15 subjects produced anti-KLH-specific IgE. KLH-specific IgG and IgA at levels similar to that seen with KLH alone could also be detected. Subjects who received DEPs and KLH had significantly increased IL-4, but not IFN-gamma, levels in nasal lavage fluid, whereas these levels were unchanged in subjects receiving KLH alone.
These studies demonstrate that DEPs can act as mucosal adjuvants to a de novo IgE response and may increase allergic sensitization.
柴油废气颗粒(DEP)可增加人上呼吸道黏膜的体内免疫球蛋白E(IgE)及细胞因子生成,加剧变应性炎症。
我们研究了暴露于DEP是否会通过引发针对新抗原——钥孔血蓝蛋白(KLH)的从头黏膜IgE反应,导致人类原发性致敏。
10名特应性受试者先用1mg KLH进行初次鼻腔免疫,随后每两周用100μg KLH进行2次鼻腔激发。然后对15名不同的特应性受试者进行相同的鼻腔KLH免疫,但在每次暴露于KLH前24小时给予DEP。
单独暴露于KLH可导致产生抗KLH IgG和IgA体液反应,在鼻液样本中可检测到。所有受试者均未出现抗KLH IgE。相比之下,在DEP预处理后再用KLH激发时,15名受试者中有9名产生了抗KLH特异性IgE。也可检测到水平与单独使用KLH时相似的KLH特异性IgG和IgA。接受DEP和KLH的受试者鼻灌洗液中的白细胞介素-4(IL-4)水平显著升高,但γ干扰素(IFN-γ)水平未升高,而单独接受KLH的受试者这些水平未发生变化。
这些研究表明,DEP可作为黏膜佐剂引发从头IgE反应,并可能增加变应性致敏。