氣道內注射負載卵白蛋白多肽的樹突狀細胞可誘導肺內炎癥_《中國呼吸與危重監護雜志》

作者：

王桂芳 , 白春學

復旦大學附屬中山醫院呼吸內科( 上海 200032)通訊作者: 王桂芳, E-mail: wang_guifang08@ 126. com;

關鍵詞：

哮喘樹突狀細胞氣道內注射

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目的探討樹突狀細胞( DCs) 作為免疫治療載體氣道內注射的可行性。方法取BALB/ c 小鼠骨髓單個核細胞, 以重組小鼠粒-巨細胞集落刺激因子( rmGM-CSF) + 重組小鼠白細胞介素4( rmIL-4) 體外誘導培養DCs。經磁珠純化后得到的DCs 用卵白蛋白323-339 氨基酸區( OVA323-339 多肽) 沖擊24 h。DC-OVA 組小鼠按每鼠2 ×106 細胞數進行小鼠氣道內接種。DC 組小鼠以DCs 直接進行氣道內接種作為陰性對照。接種后次日起以1% OVA 霧化, 連續5 d。經典哮喘模型組小鼠采用經典OVA 腹腔注射致敏及激發方法復制哮喘模型作為陽性對照。末次霧化后24 h 處死小鼠, 分析肺臟病理學表現、支氣管肺泡灌洗液( BALF) 中的細胞成分。結果 DC-OVA 組小鼠肺內呈現小支氣管及血管周圍大量炎細胞浸潤, 杯狀細胞增多, BALF 中細胞數明顯增多, 血清中OVA-特異性IgE 水平與經典復制哮喘模型組OVA-特異性IgE 水平相似[ ( 48. 22 ±4. 76) U/mL比( 52. 75 ±4. 03) U/mL, P gt;0. 05] 。采用該方法復制的模型與采用經典方法復制的哮喘模型表現相似。DC 組肺組織無明顯的炎癥, 血清中的OVA-特異性IgE 水平低于檢測的敏感度。結論體外抗原負載后的DCs 氣道內注射具有活力并能有效遞呈抗原, DCs 可能作為免疫治療的載體。

引用本文： 王桂芳,白春學. 氣道內注射負載卵白蛋白多肽的樹突狀細胞可誘導肺內炎癥. 中國呼吸與危重監護雜志, 2010, 9(6): 606-610. doi: 復制

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7.	王桂芳, 董春玲, 唐古生, 等. 一種復制小鼠哮喘模型的新方法.中國免疫學雜志, 2008 , 24: 1025-1027.
8.	Inaba K, Inaba M, Romani N, et al. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med,1992, 176: 1693-1702.
9.	董春玲, 魯繼榮, 王桂芳, 等. 哮喘小鼠肺組織水通道蛋白5 的表達及地塞米松對其的調節. 第二軍醫大學學報, 2008, 29: 126 -130.
10.	Lambrecht BN, Pauwels RA, Fazekas De St Groth B. Induction of rapid T cell activation, division, and recirculation by intratracheal injection of dendritic cells in a TCR transgenic model. J Immunol,2000, 164: 2937-2946.
11.	Lambrecht BN, Peleman RA, Bullock GR, et al. Sensitization to inhaled antigen by intratracheal instillation of dendritic cells. Clin Exp Allergy, 2000, 30 : 214-224 .
12.	Huh JC, Strickland DH, Jahnsen FL, et al. Bidirectional interactions between antigen-bearing respiratory tract dendritic cells ( DCs) and T cells precede the late phase reaction in experimental asthma: DC activation occurs in the airway mucosa but not in the lung parenchyma. J Exp Med, 2003, 198: 19-30.
13.	Wang GF, Dong CL, Tang GS, et al. Membrane water permeability related to antigen-presenting function of dendritic cells. Clin Exp Immunol, 2008, 153: 410-419 .
14.	Miller CW, Krishnaswamy N, Johnston C, et al. Severe asthma and the omalizumab option. Clin Mol Allergy, 2008, 6: 4.
15.	楊丹榕, 修清玉, 韓煥興, 等. 大鼠IgECH2 -3-FasL 融合蛋白真核表達質粒的構建. 上海醫學, 2004 , 27 : 931-932.

1. Hammad H, Lambrecht BN. Dendritic cells and epithelial cells:linking innate and adaptive immunity in asthma. Nat Rev Immunol,2008, 8: 193-204.
2. Idzko M, Hammad H, van Nimwegen, et al. Inhaled iloprost suppresses the cardinal features of asthma via inhibition of airway dendritic cell function. J Clin Invest, 2007 , 117: 464-472 .
3. Lewkowich IP, Herman NS, Schleifer KW, et al. CD4 + CD25 + T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function. J Exp Med, 2005 ,202 : 1549 -1561 .
4. van Rijt LS, Jung S, Kleinjan A, et al. In vivo depletion of lung CD11 c + dendritic cells during allergen challenge abrogates the characteristic features of asthma. J Exp Med, 2005, 201 : 981-991 .
5. von Garnier C, Wikstrom ME, Zosky G, et al. Allergic airways disease develops after an increase in allergen capture and processing in the airway mucosa. J Immunol, 2007, 179 : 5748 -5759.
6. Kool M, Lambrecht BN. Dendritic cells in asthma and COPD:opportunities for drug development. Curr Opin Immunol, 2007, 19 :701 -710.
7. 王桂芳, 董春玲, 唐古生, 等. 一種復制小鼠哮喘模型的新方法.中國免疫學雜志, 2008 , 24: 1025-1027.
8. Inaba K, Inaba M, Romani N, et al. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med,1992, 176: 1693-1702.
9. 董春玲, 魯繼榮, 王桂芳, 等. 哮喘小鼠肺組織水通道蛋白5 的表達及地塞米松對其的調節. 第二軍醫大學學報, 2008, 29: 126 -130.
10. Lambrecht BN, Pauwels RA, Fazekas De St Groth B. Induction of rapid T cell activation, division, and recirculation by intratracheal injection of dendritic cells in a TCR transgenic model. J Immunol,2000, 164: 2937-2946.
11. Lambrecht BN, Peleman RA, Bullock GR, et al. Sensitization to inhaled antigen by intratracheal instillation of dendritic cells. Clin Exp Allergy, 2000, 30 : 214-224 .
12. Huh JC, Strickland DH, Jahnsen FL, et al. Bidirectional interactions between antigen-bearing respiratory tract dendritic cells ( DCs) and T cells precede the late phase reaction in experimental asthma: DC activation occurs in the airway mucosa but not in the lung parenchyma. J Exp Med, 2003, 198: 19-30.
13. Wang GF, Dong CL, Tang GS, et al. Membrane water permeability related to antigen-presenting function of dendritic cells. Clin Exp Immunol, 2008, 153: 410-419 .
14. Miller CW, Krishnaswamy N, Johnston C, et al. Severe asthma and the omalizumab option. Clin Mol Allergy, 2008, 6: 4.
15. 楊丹榕, 修清玉, 韓煥興, 等. 大鼠IgECH2 -3-FasL 融合蛋白真核表達質粒的構建. 上海醫學, 2004 , 27 : 931-932.

《中國呼吸與危重監護雜志》

氣道內注射負載卵白蛋白多肽的樹突狀細胞可誘導肺內炎癥

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《中國呼吸與危重監護雜志》

氣道內注射負載卵白蛋白多肽的樹突狀細胞可誘導肺內炎癥

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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