Barker E, Reisfeld R A
Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
Cancer Res. 1993 Jan 15;53(2):362-7.
Neutrophils mediate the lysis of human neuroblastoma cells coated with human/mouse chimeric anti-GD2 ganglioside antibody ch14.18. This study examined the mechanism(s) by which this occurs. Neutrophil degranulation was found to be a required step for lysis, since release of granular enzymes from neutrophils correlated with the lysis of antibody-coated neuroblastoma cells. In addition, agents which block degranulation specifically inhibited this process. Antibody-dependent lysis of neuroblastoma cells was enhanced by exposing neutrophils to granulocyte-macrophage colony stimulatory factor. An increased release of lytic granular molecules was found to be responsible for this lymphokine-mediated phenomenon. Among the molecules released from neutrophil granules that were shown to be involved in neuroblastoma cell lysis were defensins, M(r) 3000-4000 neutrophil granular proteins which are known to bind and permeabilize tumor cells. In addition, cathepsin-G, a neutrophil granular protease, was demonstrated for the first time to mediate the lysis of human neuroblastoma cells. The enzymatic activity of cathepsin-G was found to be required for the lysis of these tumor cells, since phenylmethylsulfonyl fluoride blocks the lytic ability of this protein.
中性粒细胞介导被人/鼠嵌合抗GD2神经节苷脂抗体ch14.18包被的人神经母细胞瘤细胞的溶解。本研究检测了这一过程发生的机制。发现中性粒细胞脱颗粒是溶解所必需的步骤，因为中性粒细胞颗粒酶的释放与抗体包被的神经母细胞瘤细胞的溶解相关。此外，阻断脱颗粒的试剂可特异性抑制这一过程。通过将中性粒细胞暴露于粒细胞-巨噬细胞集落刺激因子，可增强神经母细胞瘤细胞的抗体依赖性溶解。发现溶细胞性颗粒分子释放增加是这种淋巴因子介导现象的原因。在已显示参与神经母细胞瘤细胞溶解的从中性粒细胞颗粒释放的分子中，有防御素，即分子量为3000 - 4000的中性粒细胞颗粒蛋白，已知其可结合肿瘤细胞并使其通透。此外，组织蛋白酶G，一种中性粒细胞颗粒蛋白酶，首次被证明可介导人神经母细胞瘤细胞的溶解。发现组织蛋白酶G的酶活性是这些肿瘤细胞溶解所必需的，因为苯甲基磺酰氟可阻断该蛋白的溶解能力。
