Kamijo Seiji, Takai Toshiro, Kuhara Takatoshi, Tokura Tomoko, Ushio Hiroko, Ota Mikiko, Harada Norihiro, Ogawa Hideoki, Okumura Ko
Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
J Immunol. 2009 Nov 15;183(10):6087-94. doi: 10.4049/jimmunol.0901039. Epub 2009 Oct 28.
Pollen is considered a source of not only allergens but also immunomodulatory substances, which could play crucial roles in sensitization and/or the exacerbation of allergies. We investigated how allergenic pollens from different plant species (Japanese cedar and Japanese cypress, which belong to the Cupressaceae family, and birch, ragweed, and grass) modulate murine bone marrow-derived dendritic cell (DC) responses and examined the effect of Cupressaceae pollen in vivo using mice. DCs were stimulated with pollen extracts or grains in the presence or absence of LPS. Cell maturation and cytokine production in DCs were analyzed by flow cytometry, ELISA, and/or quantitative PCR. Pollen extracts suppressed LPS-induced IL-12 production and the effect was greatest for birch and grass. Without LPS, pollen grains induced DC maturation and cytokine production without IL-12 secretion and the response, for which TLR 4 was dispensable, was greatest for the Cupressaceae family. Intranasal administration of Cupressaceae pollen in mice induced an elevation of serum IgE levels and airway eosinophil infiltration. Coadministration of ovalbumin with Cupressaceae pollen grains induced ovalbumin-specific IgE responses associated with eosinophil infiltration. The results suggest that modulation of DC responses by pollen differs among the plant families via (1) the promotion of DC maturation and cytokine production by direct contact and/or (2) the inhibition of IL-12 production by soluble factors. The strong DC stimulatory activity in vitro and IgE-inducing activity in mice support the clinical relevance of Cupressaceae pollen to allergies in humans.
花粉不仅被认为是过敏原的来源,也是免疫调节物质的来源,这些物质可能在过敏的致敏和/或加重过程中发挥关键作用。我们研究了来自不同植物物种的致敏花粉(属于柏科的日本柳杉和日本扁柏,以及桦树、豚草和草)如何调节小鼠骨髓来源的树突状细胞(DC)反应,并使用小鼠在体内检测了柏科花粉的作用。在有或没有LPS的情况下,用花粉提取物或花粉粒刺激DC。通过流式细胞术、ELISA和/或定量PCR分析DC中的细胞成熟和细胞因子产生。花粉提取物抑制LPS诱导的IL-12产生,对桦树和草的抑制作用最大。在没有LPS的情况下,花粉粒诱导DC成熟和细胞因子产生,但不分泌IL-12,且这种反应(TLR 4对此反应并非必需)在柏科中最为明显。给小鼠鼻内注射柏科花粉会导致血清IgE水平升高和气道嗜酸性粒细胞浸润。将卵清蛋白与柏科花粉粒共同给药会诱导与嗜酸性粒细胞浸润相关的卵清蛋白特异性IgE反应。结果表明,花粉对DC反应的调节在不同植物科之间存在差异,其方式为:(1)通过直接接触促进DC成熟和细胞因子产生,和/或(2)通过可溶性因子抑制IL-12产生。体外强大的DC刺激活性和在小鼠体内的IgE诱导活性支持了柏科花粉与人类过敏临床相关性。