Yamamoto K, Kawamura I, Ito J, Mitsuyama M
Department of Microbiology, Head and Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Clin Exp Allergy. 2006 Jun;36(6):760-9. doi: 10.1111/j.1365-2222.2006.02488.x.
It has been suggested that airway bacterial infections exacerbate allergic disorders, and bacterial components in the air affect allergic inflammation via Toll-like receptors expressed on mast cells and dendritic cells in the airway mucosa.
Peptidoglycan (PGN) is a major component of the bacterial cell wall. We investigated the effect of PGN on the effector phase of allergic inflammation, in comparison with the effect of CpG-oligodeoxynucleotides (CpG), which is known to be a Th1 adjuvant.
Ovalbumin (OVA)-sensitized mice were challenged intranasally with OVA alone or OVA together with PGN or CpG. Nasal allergic symptoms and eosinophilia were scored, and the OVA-specific cytokine response was examined in the cells of cervical lymph nodes and nasal mucosa. Bone marrow-derived mast cells (BMMCs) and dendritic cells (BMDCs) were stimulated with PGN or CpG in vitro, and the expression level of cytokines and chemokines was examined by RT-PCR. In addition, the expression level of chemokines was examined by RT-PCR in mast cells of OVA-sensitized mice challenged with OVA alone or OVA together with PGN or CpG.
PGN exposure exacerbated the nasal allergic symptoms and eosinophilia, whereas CpG exposure suppressed them. In addition, PGN exposure increased the OVA-specific IL-4 response in the cells, whereas CpG exposure decreased it. On the other hand, there were no significant differences in the OVA-specific IFN-gamma response. PGN but not CpG induced the expression of thymus and activation-regulated chemokine (TARC) and macrophage/monocyte-derived chemokine (MDC) in both BMMCs and mast cells of mice sensitized and challenged with OVA. CpG but not PGN induced the expression of IFN-beta and interferon-inducible protein-10 (IP-10) in BMDCs, and histamine did not influence this effect.
These results demonstrate that PGN exposure exacerbates allergic inflammation mainly via mast cells, whereas CpG exposure suppresses allergic inflammation mainly via dendritic cells.
有人提出气道细菌感染会加剧过敏性疾病，空气中的细菌成分通过气道黏膜中肥大细胞和树突状细胞上表达的Toll样受体影响过敏性炎症。
肽聚糖（PGN）是细菌细胞壁的主要成分。我们研究了PGN对过敏性炎症效应阶段的影响，并与已知为Th1佐剂的CpG-寡脱氧核苷酸（CpG）的作用进行比较。
用卵清蛋白（OVA）致敏的小鼠经鼻单独给予OVA或与PGN或CpG一起给予OVA。对鼻过敏症状和嗜酸性粒细胞增多进行评分，并在颈淋巴结和鼻黏膜细胞中检测OVA特异性细胞因子反应。体外用PGN或CpG刺激骨髓来源的肥大细胞（BMMC）和树突状细胞（BMDC），通过逆转录聚合酶链反应（RT-PCR）检测细胞因子和趋化因子的表达水平。此外，对单独给予OVA或与PGN或CpG一起给予OVA刺激的OVA致敏小鼠的肥大细胞，通过RT-PCR检测趋化因子的表达水平。
暴露于PGN会加剧鼻过敏症状和嗜酸性粒细胞增多，而暴露于CpG则会抑制这些症状。此外，暴露于PGN会增加细胞中OVA特异性白细胞介素-4（IL-4）反应，而暴露于CpG则会降低该反应。另一方面，OVA特异性干扰素-γ（IFN-γ）反应没有显著差异。PGN而非CpG在致敏并经OVA攻击的小鼠的BMMC和肥大细胞中诱导胸腺和活化调节趋化因子（TARC）以及巨噬细胞/单核细胞来源的趋化因子（MDC）的表达。CpG而非PGN在BMDC中诱导干扰素-β（IFN-β）和干扰素诱导蛋白10（IP-10）的表达，组胺不影响这种作用。
这些结果表明，暴露于PGN主要通过肥大细胞加剧过敏性炎症，而暴露于CpG主要通过树突状细胞抑制过敏性炎症。
