Oral administration of chitin down-regulates serum IgE levels and lung eosinophilia in the allergic mouse
Oral administration of chitin down-regulates serum IgE levels and lung eosinophilia in the allergic mouse
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DOI：
10.4049/jimmunol.164.3.1314
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发表时间：
2000-02-01
影响因子：
4.4
通讯作者：
Myrvik, QN
中科院分区：
文献类型：
--
作者：
Shibata, Y;Foster, LA;Myrvik, QN
先前的研究表明，局部巨噬细胞通过甘露糖受体吞噬非抗原几丁质颗粒（1-10 μ m的n -乙酰- d -葡萄糖胺聚合物），并产生IL-12、IL-18和tnf - α，这些细胞因子导致NK细胞产生ifn - γ。为了确定几丁质是否能下调Th2反应，我们在BALB/c和C57BL/6小鼠中口服几丁质（豚草过敏原免疫前3天和免疫后13天口服8 mg/d），这些豚草免疫小鼠在第11天气管内注射豚草，攻毒后3天，免疫小鼠的血清IgE水平和肺嗜酸性粒细胞数量增加。几丁质处理使这两种菌株的这些事件减少。为了研究抑制Th2反应的机制，我们从豚草免疫小鼠（对照）中分离脾脏细胞（4 × 10(6)个细胞/ml），在豚草和/或几丁质存在下培养3天（回忆反应），豚草单独刺激IL-4 （0.6 ng/ml）、IL-5 （20 U/ml）和IL-10 （3.2 ng/ml）的产生，但不刺激ifn - γ，豚草/几丁质刺激导致IL-4、IL-5和IL-IO水平显著降低，lfn - γ的产生（48 U/ml）。几丁质处理小鼠的脾脏细胞显示豚草刺激的ifn - γ产生（15 U/ml）和显著降低的Th2细胞因子水平，表明免疫反应被重定向到Th1反应。综上所述，这些结果表明，几丁质诱导的先天免疫反应下调了过敏小鼠中th2促进的IgE产生和肺嗜酸性粒细胞增多。
Previous studies showed that local macrophages phagocytose nonantigenic chitin particles (1-10 mu m polymers of N-acetyl-D-glucosamine) through mannose receptors and produce IL-12, IL-18, and TNF-alpha, These cytokines lead to the production of IFN-gamma by NK cells. To determine whether chitin could down-regulate Th2 responses, chitin was given orally (8 mg/day for 3 days before and 13 days during ragweed allergen immunization) in BALB/c and C57BL/6 mice, These ragweed-immunized mice were given ragweed intratracheally on day 11, Three days after the challenge, the immunized mice with saline (controls) showed increases in serum IgE levels and lung eosinophil numbers. The chitin treatment resulted in decreases of these events in both strains. To dissect the inhibitory mechanisms of Th2 responses, spleen cells (4 x 10(6) cells/ml) isolated from the ragweed-immunized mice (controls) were cultured in the presence of ragweed and/or chitin for 3 days (recall responses), Ragweed alone stimulated the production of IL-4 (0.6 ng/ml), IL-5 (20 U/ml), and IL-10 (3.2 ng/ml), but not IFN-gamma, Ragweed/chitin stimulation resulted in significant decreases of IL-4, IL-5, and IL-IO levels and the production of lFN-gamma (48 U/ml), Moreover, spleen cells isolated from the chitin-treated mice showed ragweed-stimulated IFN-gamma production (15 U/ml) and significantly lower levels of the Th2 cytokines, suggesting that the immune responses were redirected toward a Th1 response. Collectively, these results indicate that chitin-induced innate immune responses down-regulate Th2-facilitated IgE production and lung eosinophilia in the allergic mouse.