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经鼻递送截短的重组人表面活性蛋白D可有效下调对烟曲霉过敏原致敏小鼠的过敏性超敏反应。

Intranasal delivery of a truncated recombinant human SP-D is effective at down-regulating allergic hypersensitivity in mice sensitized to allergens of Aspergillus fumigatus.

作者信息

Strong P, Reid K B M, Clark H

机构信息

Medical Research Council Immunochemistry Unit, University of Oxford, UK.

出版信息

Clin Exp Immunol. 2002 Oct;130(1):19-24. doi: 10.1046/j.1365-2249.2002.01968.x.

Abstract

C57BL/6 mice were sensitized to Aspergillus fumigatus 1-week culture filtrate, which is rich in the non-glycosylated allergen Asp f1, a major allergen in allergic bronchopulmonary aspergillosis (ABPA). A comparison of the effect of treatment of allergen challenged mice by intranasal administration of a 60-kDa truncated recombinant form of human SP-D (rfhSP-D) or recombinant full length SP-A (rhSP-A) was undertaken. Treatment with rfhSP-D produced significant reduction in IgE, IgG1 and peripheral blood eosinophilia and treatment with rfhSP-D, but not rhSP-A resulted in a significant reduction in airway hyperresponsiveness as measured by whole body plethysmography. Lung histology revealed less peribronchial lymphocytic infiltration in mice treated with rfhSP-D. Intracellular cytokine staining of spleen homogenates showed increases in IL-12 and IFN-gamma and decrease in IL-4. The level of endogenous mouse SP-D was elevated sixfold in the lungs of sensitized mice and was not affected by treatment with rfhSP-D. Taken with our previous studies, with a BALB/c mouse model of ABPA using a 3-week A. fumigatus culture filtrate, the present results show that rfhSP-D can suppress the development of allergic symptoms in sensitized mice independent of genetic background and using a different preparation of A. fumigatus allergens.

摘要

将C57BL/6小鼠对烟曲霉1周龄培养滤液进行致敏,该滤液富含非糖基化变应原Asp f1,这是变应性支气管肺曲霉病(ABPA)中的一种主要变应原。对经变应原激发的小鼠通过鼻内给予60 kDa截短的重组人SP-D(rfhSP-D)或重组全长SP-A(rhSP-A)进行治疗的效果进行了比较。用rfhSP-D治疗可使IgE、IgG1和外周血嗜酸性粒细胞显著减少,并且用rfhSP-D而非rhSP-A治疗可使通过全身体积描记法测量的气道高反应性显著降低。肺组织学显示,用rfhSP-D治疗的小鼠支气管周围淋巴细胞浸润较少。脾匀浆的细胞内细胞因子染色显示IL-12和IFN-γ增加,IL-4减少。致敏小鼠肺内内源性小鼠SP-D水平升高了6倍,且不受rfhSP-D治疗的影响。结合我们之前使用3周龄烟曲霉培养滤液的BALB/c小鼠ABPA模型的研究,目前的结果表明,rfhSP-D可抑制致敏小鼠变应性症状的发展,且与遗传背景无关,并使用了不同制备的烟曲霉变应原。

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