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(yǎng)DCs。經磁珠純化后得到的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(xù)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(fā)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(jiān)護雜志, 2010, 9(6): 606-610. doi: 復制
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| 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(jié). 第二軍醫(yī)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(yī)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(jié). 第二軍醫(yī)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(yī)學, 2004 , 27 : 931-932.