Dendritic CellsOverloaded Antigens Injected Intratracheally Induce Lung Inflammation_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

WANGGuifang , BAI Chunxue

Department of Respiratory Medicine, Zhongshan Hospital, Fudan University. Shanghai,200003, ChinaCorresponding Author: WANG Gui-fang, E-mail: wang_guifang08@ 126. com;

Corresponding author：

Keywords：

Asthma; Dendritic cells; Intratracheal injection

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Objective To investigate the feasibility of dendritic cells ( DCs ) as vector of immunotherapy through intratracheal injection. Methods The DCs obtained from the bone marrow of BALB/ c mice were cultured and isolated with CD11c-positive magnetic beads. Then DCs were overloaded with ovalbumin peptide 323-339 ( OVA 323-339) for 24 hours. The mice in the DC-OVA group were intratrachelly injected DCs overloaded with OVA 323-339 in dose of 2 ×106 cells per mouse. The mice in the
negative control group were intratracheally injected with DCs untreated by OVA 323-339. On the second day,all mice were challenged with 1% OVA in PBS lasting for five days. The asthma animal model established by classic method was used for the positive control. Pathologic changes in lung and cell numbers in bronchoalveolar lavage fluid ( BALF) were assayed 24 hours after challenged. Results Just like the lung tissues from the mice asthma models, the lung tissues from the mice instilled with DCs overloaded with allergen OVA 323-339 showed extensive inflammatory cells infiltration, most of which were eosinophils, neutrophils and lymphocytes. The lung tissues in the DC group showed no obvious inflammation. There were more cells in BALF in the DC-OVA group than that in the DC group. OVA-specific IgE in serum from the DC-OVA group was not significantly different from that in the mice asthma models [ ( 48. 22 ±4. 76) U/mL vs. ( 52. 75 ±4. 03) U/mL, P gt;0. 05] . Conclusion DCs overloaded antigen has the ability of transferring of antigen effectively and may be used as vectors of immunotherapy.

Citation： WANGGuifang,BAI Chunxue. Dendritic CellsOverloaded Antigens Injected Intratracheally Induce Lung Inflammation. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(6): 606-610. doi: Copy

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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, 鲁继荣, 王桂芳, 等. 哮喘小鼠肺组织水通道蛋白5 的表达及地塞米松对其的调节. 第二军医大学学报, 2008, 29: 126 -130.
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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.	杨丹榕, 修清玉, 韩焕兴, 等. 大鼠IgECH2 -3-FasL 融合蛋白真核表达质粒的构建. 上海医学, 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. 一种复制小鼠哮喘模型的新方法.中国免疫学杂志, 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, 鲁继荣, 王桂芳, 等. 哮喘小鼠肺组织水通道蛋白5 的表达及地塞米松对其的调节. 第二军医大学学报, 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. 杨丹榕, 修清玉, 韩焕兴, 等. 大鼠IgECH2 -3-FasL 融合蛋白真核表达质粒的构建. 上海医学, 2004 , 27 : 931-932.

Chinese Journal of Respiratory and Critical Care Medicine

Dendritic CellsOverloaded Antigens Injected Intratracheally Induce Lung Inflammation

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