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Effects of β2 Receptor Agonist on Dendritic Cells of Asthma

Author: ZhuRong
Tutor: BaiChong
School: Second Military Medical University
Course: Internal Medicine
Keywords: asthma dendritic cell salbutamol T lymphcell cytokine
CLC: R562.25
Type: Master's thesis
Year: 2008
Downloads: 64
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Abstract

Effects ofβ2 Receptor Agonist on Dendritic Cells of AsthmaAsthma is a frequent disease of respiratory system.With the development of social industrialization and atmospheric pollution,the global disease incidence is rising gradually.β2 receptor agonist is a orthodox medicine that can act onβ2 receptor of respiratory tract, activate adenylate cyclase and increase the level of cyclic Adenosine monophosphate and reduce the level of liber Ca²⁺,leading to the laxation of bronchus smooth muscle.And it can relive the respiratory spasm through repressing allergic response cytokine released from mast cells.We assume whetherβ2 receptor agonist can act in（dendritic cells）DCs or not.Therefore,in this experimentation we can observe the function alteration of DCs after the administration ofβ2 receptor agonist to the asthma mice models.Objective:Through the research about the influence ofβ2 receptor agonist on superficial molecule of DCs of lung of asthma mice and induced the ability of proliferation and differentiation of T lymphocyte,we can prove asthma can be treated with salbutamol and we analyse these therapeutic actions are implemented through DCs.Methods:Eighty female BALB/C mice aged 4-6 week were divided into five groups randomly and averagely.The four groups were made into mouse models of asthma except the normal control group.After producing mouse models of asthma according to the previous method, the asthma mice were treated with aerosol of salbutamol or dexamethasone or salbutamol plus dexamethasone or normal sodium respectively.Alternatively,animals underwent the anesthesia and the ligation of inferior lobe of fight lung and the bronchoalveolar lavage after the last aerosol exposure of the medicine above.After the bronchoalveolar lavage fluid was collected and centrifuged,the supernatant was acquired and determined the level of interleukin 4 and interleukin 5.The inferior lobe of right lung were sheared and immersed into formalin.Afterward,they will be used in pathological section.The blood serum of remaining mouse models was collected and detected the level of immunoglobulin E.All lungs of remaining mouse models were collected and digested with collagenaseⅡand DCs were purified by using the monoclonal mouse CD11c antibodies and the magnetic beads.Through flow cytometry,we may detect the expression of MHCⅡ,CD80 and CD86. The OVA specific TCR transgenic CD90⁺ T cells obtained from DO11.10 mice were cultured with the lung DCs of the mouse models in vitro.The production of IL-4 and IL-5 was assayed by the enzyme linked immunosorbent assay.Through the lipid scintillation, the proliferative response of T leukomonocyte was detected.Results:1、After hematoxylin-eosin staining,it was thus that a great quantity inflammatory cells infiltrating and the smooth muscles of bronchus thickening and the hyperplasia of beaker cells in the lung issue of the group which were treated with aerosol of normal saline, on the contrary,the appearances above were not conspicuous in other groups. 2、The level of immunoglobulin E in the blood serum of asthma model was all increased and the group which were treated with aerosol of normal saline was higher than other groups.The level of immunoglobulin E in the blood serum of normal control group was very low.3、The level of interleukin 4 and interleukin 5 in the bronchoalveolar lavage fluid of the group which were treated with aerosol of normal saline was the highest in all groups.4、The expression of costimulatory molecules（CD80、CD86 and MHCⅡ） was upper-regulated in the group which were treated with aerosol of normal saline than other groups.5、When lung DC and OVA-special T leukomonocyte from DO11.10 were cultured together,the proliferative responses in the group which were treated with aerosol of normal saline were the most obvious in all groups.There is no proliferative responses in the normal control group.6、The level of interleukin 4 and interleukin 5 in the culture fluid of DC and the OVA-special T leukomonocyte in the group which were treated with aerosol of normal saline was the highest in all groups. Conclusions:1、Salbutamol can improve pathological changes of mouse models of asthma.2、Salbutamol can down-regulate the CD80、CD86 and MHCⅡmolecule expression of DCs.3、Salbutamol can cut down the incentive ability of T leukomonocyte through DCs.4、Salbutamol can restrain the production of Th2 cytokine.In a word,salbutamol can reverse the Th2-deviated immune response through DCs.

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CLC: > Medicine, health > Internal Medicine > Respiratory system and chest diseases > Trachea and bronchial disease > Bronchial disease > Bronchial asthma
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