• 復(fù)旦大學(xué)附屬中山醫(yī)院呼吸內(nèi)科( 上海 200032)通訊作者: 王桂芳, E-mail: wang_guifang08@ 126. com;

目的  探討樹(shù)突狀細(xì)胞( DCs) 作為免疫治療載體氣道內(nèi)注射的可行性。方法  取BALB/ c 小鼠骨髓單個(gè)核細(xì)胞, 以重組小鼠粒-巨細(xì)胞集落刺激因子( rmGM-CSF) + 重組小鼠白細(xì)胞介素4( rmIL-4) 體外誘導(dǎo)培養(yǎng)DCs。經(jīng)磁珠純化后得到的DCs 用卵白蛋白323-339 氨基酸區(qū)( OVA323-339 多肽) 沖擊24 h。DC-OVA 組小鼠按每鼠2 ×106 細(xì)胞數(shù)進(jìn)行小鼠氣道內(nèi)接種。DC 組小鼠以DCs 直接進(jìn)行氣道內(nèi)接種作為陰性對(duì)照。接種后次日起以1% OVA 霧化, 連續(xù)5 d。經(jīng)典哮喘模型組小鼠采用經(jīng)典OVA 腹腔注射致敏及激發(fā)方法復(fù)制哮喘模型作為陽(yáng)性對(duì)照。末次霧化后24 h 處死小鼠, 分析肺臟病理學(xué)表現(xiàn)、支氣管肺泡灌洗液( BALF) 中的細(xì)胞成分。結(jié)果  DC-OVA 組小鼠肺內(nèi)呈現(xiàn)小支氣管及血管周?chē)罅垦准?xì)胞浸潤(rùn), 杯狀細(xì)胞增多, BALF 中細(xì)胞數(shù)明顯增多, 血清中OVA-特異性IgE 水平與經(jīng)典復(fù)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(fù)制的模型與采用經(jīng)典方法復(fù)制的哮喘模型表現(xiàn)相似。DC 組肺組織無(wú)明顯的炎癥, 血清中的OVA-特異性IgE 水平低于檢測(cè)的敏感度。結(jié)論  體外抗原負(fù)載后的DCs 氣道內(nèi)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(xué). 氣道內(nèi)注射負(fù)載卵白蛋白多肽的樹(shù)突狀細(xì)胞可誘導(dǎo)肺內(nèi)炎癥. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2010, 9(6): 606-610. doi: 復(fù)制

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(fù)制小鼠哮喘模型的新方法.中國(guó)免疫學(xué)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(dá)及地塞米松對(duì)其的調(diào)節(jié). 第二軍醫(yī)大學(xué)學(xué)報(bào), 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(dá)質(zhì)粒的構(gòu)建. 上海醫(yī)學(xué), 2004 , 27 : 931-932.
  1. 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. 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. 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. 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. 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. 6. Kool M, Lambrecht BN. Dendritic cells in asthma and COPD:opportunities for drug development. Curr Opin Immunol, 2007, 19 :701 -710.
  7. 7. 王桂芳, 董春玲, 唐古生, 等. 一種復(fù)制小鼠哮喘模型的新方法.中國(guó)免疫學(xué)雜志, 2008 , 24: 1025-1027.
  8. 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. 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(dá)及地塞米松對(duì)其的調(diào)節(jié). 第二軍醫(yī)大學(xué)學(xué)報(bào), 2008, 29: 126 -130.
  10. 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. 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. 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. 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. 14. Miller CW, Krishnaswamy N, Johnston C, et al. Severe asthma and the omalizumab option. Clin Mol Allergy, 2008, 6: 4.
  15. 15. 楊丹榕, 修清玉, 韓煥興, 等. 大鼠IgECH2 -3-FasL 融合蛋白真核表達(dá)質(zhì)粒的構(gòu)建. 上海醫(yī)學(xué), 2004 , 27 : 931-932.