嗜酸性粒细胞的抗白血病肿瘤免疫功能的探讨  

The immunological effect of anti-leukemic tumor induced by eosinophilic granulocyte

作　　者：孙黎飞 吴强强 郝红峰 马向杉 杜延会 王桂臣 张金标 

机构地区：[1]255300山东淄博,解放军第一四八中心医院济南军区肿瘤诊疗专科中心

出　　处：《中华内科杂志》2013年第5期395-399,共5页Chinese Journal of Internal Medicine

基　　金：济南军区＂十二五＂重点支持项目（JN11L017）

摘　　要：目的 探讨嗜酸性粒细胞（EOS）在慢性粒细胞白血病（CML）患者骨髓中的抗肿瘤细胞免疫功能.方法 逆转录PCR观察CML患者外周血纯化EOS的BCR-ABL融合基因、IL-12 mRNA和IL-17 mRNA表达情况.酶联免疫吸附试验检测CML患者血清中IL-12和IL-17浓度；观察患者骨髓EOS中过氧化物酶（POX）和人类白细胞抗原（HLA）-DR表达,免疫荧光观察患者骨髓涂片中EOS甘露糖受体（MR）、IL-12、IL-17A和IL-17RA表达水平,并与正常健康人群对比.结果 60例CML患者血清IL-12和IL-17水平分别为（196.33 ±21.79） ng/L和（36.55±3.01） ng/L,明显高于对照组的（96.60 ±4.92） ng/L和（23.74±1.36） ng/L（P值均＜0.01）.32例骨髓EOS活化组患者IL-12和IL-17的水平分别为（273.12±17.16） ng/L和（40.11±6.13） ng/L,显著高于EOS未活化组的（126.16±14.27） ng/L和（28.14±5.29）ng/L（P值均＜0.01）.EOS表达IL-12和IL-17 mRNA,不表达BCR-ABL融合基因.CML骨髓和外周血EOS明显增多,胞浆内POX强阳性,弱表达HLA-DR,以黏附、捕获和吞噬状态攻击肿瘤细胞.活化状态的EOS高表达MR、IL-12、IL-17A和IL-17RA,与患者血清细胞因子水平密切相关.结论 CML骨髓中活化的EOS表达IL-12 mRNA和IL-17 mRNA,可通过释放POX、分泌IL-12和IL-17介导细胞免疫和炎症反应破坏白血病肿瘤细胞；通过表达MR捕获和吞噬细胞,在CML患者体内发挥重要的抗肿瘤免疫生物学效应.Objective To investigate the biological effect of anti-leukemic cells induced by eosinophilic granulocyte （EOS） in bone marrow of patients with chronic myelogcnous leukemia （CML）. Methods The BCR-ABL fusion gene as well as the expression of IL-12 and IL-17 mRNA were performed by RT-PCR. The serum concentrations of eytokine 1L-12 and IL-17 were determined by enzyme-linked immuno sorbent assay （ELISA）. Immunochemistry staining and cytochemistry staining were used to observe the peroxydase （POX） and human leukocyte antigen （HLA）-DR expression of EOS in bone marrow. Immunofluoresceucc staining was used to observe mannose receptor （MR）, IL-12, IL-17A and IL-17 receptor A （IL-17RA） expression of EOS. The results between the CML patients and the healthy controls were compared. Results Serum levels of IL-12 and IL-17 were higher in the 60 CML patients [ （ 196. 33 ±21.79） ng/L and （36. 55±3. O1 ） ng/L] than those in the controls [ （96. 60 ±4. 92） ng/L and （23.74 ± 1.36） ng/L]. In the 32 patients with activated EOS, the levels of IL-12 and IL-17 were （273. 12± 17. 16） ng/L and （40. 11± 6. 13 ） ng/L, which were significantly higher than those in the non-activated EOS [（126.16±14.27） ng/Land （28.14 ±5.29） ug/L] （Pvalues〈0.01）. IL-12 and IL-17 mRNA were expressed in activated EOS, while BCR-ABL fusion gene was not found. The amounts of EOS were increased abnormally in the bone marrow and peripheral blood of the CML patients with POX positive staining in the cytoplasm and weakly positive HLA-DR staining. It was observed easily by a microscope that EOS could attack leukemic cells in bone marrow through adhesion, capture and phagocytosis. Activated EOS could express IL-12, IL-17A and MR, which was related with the serum levels of these cytokines. Conclusions Activated EOS in bone marrow of CML patients could express IL-12 and IL-17. Activated EOS could induce coup injury to leukemic cell by releasing POX and expressing IL-12 and IL-17. It can also capture

关 键 词：嗜酸细胞 白血病 粒细胞 慢性 IL-17 IL-12 甘露糖受体 

分 类 号：R733[医药卫生—肿瘤]