过继转移日本血吸虫感染鼠DC对OVA诱导的肺病变的实验研究
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摘要
目的探讨过继转移日本血吸虫感染鼠树突状细胞(DC)对OVA诱导的肺组织细胞CCL-11、IL-13Ra2表达及嗜酸性粒细胞浸润的影响。方法用CD11c+磁珠分离纯化日本血吸虫感染鼠及正常鼠DC亚群CD11c+细胞。取30只BALB/c小鼠,雌性,7周龄,将其随机分成6组,每组5只,A组为正常对照组(N组),B组为单纯哮喘组(OVA组),C大组为预防组(由C1、C2两组组成),其中C1组为过继转移血吸虫感染鼠DC后诱发哮喘组(SJDC/OVA组),C2组为过继转移正常鼠DC后诱发哮喘组(NDC/OVA组),D大组为治疗组(由D1、D2两组组成),D1组为诱发哮喘后过继转移血吸虫感染鼠DC组(OVA/SJDC),D2组为诱发哮喘后过继转移正常鼠DC组(OVA/NDC)。过继转移前3周开始用OVA腹腔致敏D组小鼠诱发哮喘,过继转移当日以不含蛋白的PBS洗涤纯化的CDllc+细胞,通过尾静脉过继转移给C1、C2、D1、D2四组小鼠,每只小鼠过继转移1×106个CDllc+细胞,其中C1、D1组过继转移血吸虫感染小鼠DC,C2、D2组过继转移正常小鼠DC。30min后D组小鼠经鼻滴入50μg OVA,连续7天,而后处死取材。过继转移2小时后开始诱发B、C1、C2组小鼠哮喘,最后一次经鼻滴入OVA24小时后,处死小鼠,取小鼠肺组织作病理切片及免疫组化切片,观察其炎症变化和CCL-11、IL-13Ra2的表达。结果肺部病理HE染色结果显示,C1、D1组小鼠炎症较轻；B、C2、D2组炎症明显,大量炎细胞浸润。A、B、C1、C2、D1、D2组小鼠肺组织免疫组化染色显示,CCL-11在小鼠肺组织中血管、气管内的阳性区域面积占血管、气管总面积的百分比分别为0.1653±0.0214、0.5339±0.0322、0.2737±0.0218、0.4818±0.0199、0.2397±0.0239、0.4857±0.0141,CCL-11在小鼠肺组织中阳性区域平均光密度值分别为0.1674±0.0104、0.3874±0.0236、0.3160±0.0235、0.3082±0.0197、0.2546±0.0172、0.2398±0.0121; IL-13Ra2在小鼠肺组织中血管、气管内的阳性区域面积占血管、气管总面积的百分比分别为0.1722±0.0108、0.5440±0.0281、0.2543±0.0341、0.4470±0.0330、0.4994±0.0304、0.3051±0.0198、IL-13Ra2在小鼠肺组织中阳性区域平均光密度值分别为0.1746±0.0090、0.4014±0.0130.0.3266±0.0144、0.4228±0.0058、0.2808±0.0102、0.2566±0.0093.与B、C2组比较,C1组CCL-11、IL-13Ra2在小鼠肺组织中血管、气管内的阳性区域面积占血管、气管总面积的百分比及阳性区域平均光密度值明显下降(P<0.05)；与B、D2组比较,D1组CCL-11、IL-13Ra2在小鼠肺组织中血管、气管内的阳性区域面积占血管、气管总面积的百分比及阳性区域平均光密度值明显下降(P<0.05)。结论血吸虫感染鼠的DC对OVA诱导的过敏性哮喘有明显的抑制作用,提示其对哮喘具有预防和治疗作用。
Objective This paper aimed at studying the effect of dendritic cells (DCs), which were adoptively transferred from Schistosoma japonicum-infected mice, on the expression of CCL-11 and IL-13Ra2 and the infiltration of EOS induced by OVA in lung tissue. Methods DCs of Schistosoma japonicum-infected mice and naive mice were respectively isolated and purified using CD11c+ microbeads.30 female BALB/ c mice (7-week old) were randomly divided into 6 groups (5 mice/group).The mice in Group A were naive mice. The mice in Group B were OVA-treated only. Group C included Group C1 and Group C2.The mice in Group C1 were OVA-treated after adoptive transfer of DCs of Schistosoma japonicum-infected mice (SJDC/OVA).The mice in Group C2 were OVA-treated after adoptive transfer of DCs of naive mice (NDC/OVA).Group D included Group D1 and Group D2.The mice in Group D1 were adoptively transferred with DCs of Schistosoma japonicum-infected mice after OVA treatment(OVA/SJDC).The mice in Group D2 were adoptively transferred with DCs of naive mice after OVA treatment (OVA/NDC). The mice in Group D were sensitized with OVA.3 weeks after sensitization, purified CD11c+ cells were first washed in protein-free PBS,and then injected into the tail vein of the mice in Group C1,C2, D1 and D2(1×106/mouse). The mice in Group C1 and D1 received DCs of Schistosoma japonicum-infected mice, while the mice in Group C2 and D2 received DCs of naive mice.30 minutes later, the mice in Group D were challenged intranasally with 50μg OVA for 7 consecutive days, and then the mice were killed and their lungs were collected for further analysis.2 hours following adoptive transfer, the mice in Group B, C1 and C2 were sensitized and challenged with OVA in the same manner.24 hours following the last challenge, the mice in Group A, B,C1 and C2 were sacrificed, and their lungs werecollected. The lungs of the mice in all six groups would be used for histological and immunohistochemical analysis. Results Histological analysis showed that pulmonary inflammation of the mice in Group C1 and D1 diminished markedly, compared with the mice in Group B,C2 and D2(P< 0.05).Immunohistochemical analysis showed that, for the mice in Group A, B,C1,C2, D1 and D2,the percentage of the positive area of CCL-11 in the blood vessels and tracheas in lung tissue were successively 0.1653±0.0214,0.5339±0.0322, 0.2737±0.0218,0.4818±0.0199,0.2397±0.0239 and 0.4857±0.0141;The average optical density (AOD) of the positive area of CCL-11 in the blood vessels and tracheas in lung tissue were successively 0.1674±0.0104, 0.3874±0.0236,0.3160±0.0235,0.3082±0.0197,0.2546±0.0172 and 0.2398±0.0121; the percentage of the positive area of IL-13Ra2 in the blood vessels and tracheas in lung tissue were successively 0.1722±0.0108,0.5440±0.0281,0.2543±0.0341, 0.4470±0.0330,0.4994±0.0304 and 0.3051±0.0198;AOD of the positive area of IL-13Ra2 in the blood vessels and tracheas in lung tissue were successively 0.1746±0.0090,0.4014±0.0130,0.3266±0.0144,0.4228±0.0058,0.2808±0.0102 and 0.2566±0.0093.Compared with the mice in Group B and C2, AOD and the percentage of the positive area of CCL-11 and IL-13Ra2 of the mice in Group C1 significantly decreased(P<0.05);Compared with the mice in Group B and D2, AOD and the percentage of the positive area of CCL-11 and IL-13Ra2 of the mice in Group D1 reduced markedly(P<0.05).Conclusion DCs of Schistosoma japonicum-infected mice played a critical role in the inhibition of OVA-induced allergic asthma, which indicating their preventive and therapeutic functions on asthma.
Objective This paper aimed at studying the effect of dendritic cells (DCs), which were adoptively transferred from Schistosoma japonicum-infected mice, on the expression of CCL-11 and IL-13Ra2 and the infiltration of EOS induced by OVA in lung tissue. Methods DCs of Schistosoma japonicum-infected mice and naive mice were respectively isolated and purified using CD11c+ microbeads.30 female BALB/ c mice (7-week old) were randomly divided into 6 groups (5 mice/group).The mice in Group A were naive mice. The mice in Group B were OVA-treated only. Group C included Group C1 and Group C2.The mice in Group C1 were OVA-treated after adoptive transfer of DCs of Schistosoma japonicum-infected mice (SJDC/OVA).The mice in Group C2 were OVA-treated after adoptive transfer of DCs of naive mice (NDC/OVA).Group D included Group D1 and Group D2.The mice in Group D1 were adoptively transferred with DCs of Schistosoma japonicum-infected mice after OVA treatment(OVA/SJDC).The mice in Group D2 were adoptively transferred with DCs of naive mice after OVA treatment (OVA/NDC). The mice in Group D were sensitized with OVA.3 weeks after sensitization, purified CD11c+ cells were first washed in protein-free PBS,and then injected into the tail vein of the mice in Group C1,C2, D1 and D2(1×106/mouse). The mice in Group C1 and D1 received DCs of Schistosoma japonicum-infected mice, while the mice in Group C2 and D2 received DCs of naive mice.30 minutes later, the mice in Group D were challenged intranasally with 50μg OVA for 7 consecutive days, and then the mice were killed and their lungs were collected for further analysis.2 hours following adoptive transfer, the mice in Group B, C1 and C2 were sensitized and challenged with OVA in the same manner.24 hours following the last challenge, the mice in Group A, B,C1 and C2 were sacrificed, and their lungs werecollected. The lungs of the mice in all six groups would be used for histological and immunohistochemical analysis. Results Histological analysis showed that pulmonary inflammation of the mice in Group C1 and D1 diminished markedly, compared with the mice in Group B,C2 and D2(P< 0.05).Immunohistochemical analysis showed that, for the mice in Group A, B,C1,C2, D1 and D2,the percentage of the positive area of CCL-11 in the blood vessels and tracheas in lung tissue were successively 0.1653±0.0214,0.5339±0.0322, 0.2737±0.0218,0.4818±0.0199,0.2397±0.0239 and 0.4857±0.0141;The average optical density (AOD) of the positive area of CCL-11 in the blood vessels and tracheas in lung tissue were successively 0.1674±0.0104, 0.3874±0.0236,0.3160±0.0235,0.3082±0.0197,0.2546±0.0172 and 0.2398±0.0121; the percentage of the positive area of IL-13Ra2 in the blood vessels and tracheas in lung tissue were successively 0.1722±0.0108,0.5440±0.0281,0.2543±0.0341, 0.4470±0.0330,0.4994±0.0304 and 0.3051±0.0198;AOD of the positive area of IL-13Ra2 in the blood vessels and tracheas in lung tissue were successively 0.1746±0.0090,0.4014±0.0130,0.3266±0.0144,0.4228±0.0058,0.2808±0.0102 and 0.2566±0.0093.Compared with the mice in Group B and C2, AOD and the percentage of the positive area of CCL-11 and IL-13Ra2 of the mice in Group C1 significantly decreased(P<0.05);Compared with the mice in Group B and D2, AOD and the percentage of the positive area of CCL-11 and IL-13Ra2 of the mice in Group D1 reduced markedly(P<0.05).Conclusion DCs of Schistosoma japonicum-infected mice played a critical role in the inhibition of OVA-induced allergic asthma, which indicating their preventive and therapeutic functions on asthma.
引文
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