HUMAN MONOCYTE ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY TO TUMOR-CELLS
HUMAN MONOCYTE ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY TO TUMOR-CELLS
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DOI：
10.1172/jci109236
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发表时间：
1978-01-01
影响因子：
15.9
通讯作者：
LOBUGLIO, AF
中科院分区：
文献类型：
--
作者：
SHAW, GM;LEVY, PC;LOBUGLIO, AF
以往对肿瘤细胞的单核细胞抗体依赖细胞介导的细胞毒性(ADCC)的研究表明，在这种细胞毒性反应中，K[胸腺来源的]淋巴细胞而不是单核细胞是活跃的。然而，这份报告表明，人单核细胞能够对3种不同的人类肿瘤细胞系(CEM T[胸腺来源的]淋巴母细胞、Raji骨髓来源的(B)淋巴母细胞和HeLa[宫颈癌]细胞)进行ADCC。溶胞作用依赖于温度，且迅速，大部分溶胞发生在孵化的前4h。裂解的程度与单核细胞(效应细胞)的数量和靶细胞的抗体致敏程度直接相关。通过对竞争的非特异性单体免疫球蛋白的抑制，以及“无辜旁观者”实验中单核细胞裂解抗体包裹的靶细胞而不是非抗体包裹的靶细胞的能力，证实了细胞溶解事件的抗体依赖的细胞接触介导的性质。单核细胞明显是单核细胞制剂中的效应细胞的证据包括：将效应细胞与调理酵母多糖颗粒预先孵育可消除单核细胞的ADCC，但对淋巴细胞ADCC的影响不大。没有证据表明Fc受体K淋巴细胞被单核细胞制剂污染，使用被抗体包裹的靶细胞被淋巴细胞选择性地裂解，而不是单核细胞。针对肿瘤细胞靶点的ADCC可能是正常和疾病状态下单核细胞功能的有用测试。
Previous investigations of mononuclear cell antibody-dependent cell-mediated cytotoxicity (ADCC) toward tumor cells suggest that K [thymus derived] lymphocytes and not monocytes are active in this cytotoxic reaction. This report, however, demonstrates that human monocytes are able to carry out ADCC toward 3 different human tumor cell lines (CEM T [thymus derived] lymphoblasts, Raji bone marrow-derived (B) lymphoblasts and HeLa[cervical carcinoma] cells). The cytolytic event was temperature dependent and rapid, with most of the lysis occurring in the first 4 h of incubation. The extent of lysis was directly related to the number of monocytes (effector cells) and to the degree of antibody sensitization of the target cells. The antibody-dependent cell contact-mediated nature of the cytolytic event was confirmed by inhibition with competing nonspecific monomeric immunoglobulin and by the ability of monocytes in "innocent bystander" experiments to lyse antibody-coated targets but not nonantibody-coated target cells. Evidence that monocytes were clearly the effector cells in the monocyte preparations included the observation that preincubation of effector cells with opsonized zymosan particles abolished ADCC by monocytes, but had little effect on lymphocyte ADCC. No evidence for Fc receptor K lymphocyte contamination of the monocyte preparations was found using antibody-coated target cells that were selectively lysed by lymphocytes but not monocytes. AdCC toward tumor cell targets may be a useful assay of monocyte function in normal and disease states.