Effect of picibanil (OK432) on neutrophil-mediated antitumor activity: implication of monocyte-derived neutrophil-activating factors.
Effect of picibanil (OK432) on neutrophil-mediated antitumor activity: implication of monocyte-derived neutrophil-activating factors.
复制标题
picibanil (OK432) 对中性粒细胞介导的抗肿瘤活性的影响：单核细胞衍生的中性粒细胞激活因子的影响。
DOI：
10.1007/bf01789335
复制
发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Shaio,MF
中科院分区：
文献类型：
--
作者：
Yang,KD;Stone,RM;Lee,CS;Chao,TY;Cheng,SN;Shaio,MF
Picibanil (OK432) 是一种链球菌提取物，已广泛用于治疗恶性腹水和胸腔积液。据信抗肿瘤机制包括补体介导的中性粒细胞激活。采用肌动蛋白聚合的流式细胞术分析作为细胞激活的指标以及肿瘤增殖测定，我们发现单核细胞源性中性粒细胞激活因子参与 OK432 诱导的中性粒细胞激活以及抗肿瘤活性。 OK432 刺激的（0.1 KE/ml；0.01 mg/ml）单核细胞上清液 (OKMS) 诱导中性粒细胞肌动蛋白聚合和趋化性。 OKMS 负责中性粒细胞介导的人白血病 (CEM) 细胞增殖抑制，并在 CEM 白血病细胞存在的情况下刺激中性粒细胞以高于 20/1 的效应/靶标比率产生超氧化物。相反，单独的OK432、OK432刺激的淋巴细胞上清液或OK432刺激的中性粒细胞上清液对中性粒细胞活化或肿瘤细胞增殖的抑制没有作用。 OK432与单核细胞联合也没有抑制CEM细胞增殖的作用。 OKMS 在 56°C 预处理 30 分钟不会影响其激活中性粒细胞的能力，这意味着补体激活不是中性粒细胞激活的原因。通过酶联免疫吸附测定和放射免疫测定测定，来自 OK432 刺激的单核细胞的上清液含有高水平的白细胞介素 8 (IL-8；1567±145 pg/ml) 和肿瘤坏死因子 (TNFα；2105±152 pg/ml)、低水平的白三烯 B4 (800±45 pg/ml) 和 IL-1β (180±22pg/ml)，但未检测到干扰素γ。 IL-1β、IL-8 和 TNFα 转录物在未经处理的单核细胞中检测不到，但在暴露于 OK432 30-60 分钟后显着增加。这些结果表明，来自单核细胞或常驻巨噬细胞的中性粒细胞激活因子可能在 OK432 诱导的中性粒细胞激活和抗肿瘤活性中发挥重要作用。
Picibanil (OK432), an extract from streptococci, has been widely utilized to treat malignant ascites and pleural effusions. The antitumor mechanism is believed to include complement-mediated neutrophil activation. Employing a flow-cytometric analysis of actin polymerization as an indicator of cell activation as well as a tumor proliferation assay, we have found that monocytederived neutrophil-activating factors were involved in OK432-induced neutrophil activation as well as antitumor activity. OK432-stimulated (0.1 KE/ml; 0.01 mg/ml) monocyte supernatants (OKMS) induced neutrophil actin polymerization and chemotaxis. OKMS were responsible for neutrophil-mediated inhibition of human leukemic (CEM) cell proliferation and stimulated neutrophils to produce superoxide in the presence of CEM leukemic cells at an effector/target ratio higher than 20/1. In contrast, OK432 alone, OK432-stimulated lymphocyte supernatants, or OK432-stimulated neutrophil supernatants had no effect on neutrophil activation or suppression of tumor cell proliferation. OK432 in combination with mononuclear cells also had no effect on the inhibition of CEM cell proliferation. Pretreatment of OKMS at 56°C for 30 min did not affect its ability to activate neutrophils, implying that complement activation is not responsible for the neutrophil activation. Supernatants from OK432-stimulated mononuclear cells, as determined by enzyme-linked immunosorbent assays and radioimmunoassays, contained high levels of interleukin-8 (IL-8; 1567±145 pg/ml) and tumor necrosis factor (TNFα; 2105±152 pg/ml), low levels of leukotriene B4 (800±45 pg/ml) and IL-1β (180±22 pg/ml), but interferon γ was not detectable. IL-1β, IL-8, and TNFα transcripts, undetectable in untreated monocytes, increased significantly after 30–60 min exposure to OK432. These results suggest that neutrophil-activating factors from monocytes or resident macrophages may play an important role in the OK432-induced neutrophil activation and antitumor activity.