Lichtenstein A, Ganz T, Selsted M E, Lehrer R I
Blood. 1986 Dec;68(6):1407-10.
We examined the activity of defensins, cysteine-rich cationic peptides that are abundant in the cytoplasmic granules of human and rabbit granulocytes, against various tumor targets. The three human defensins, HNP-1, HNP-2, and HNP-3, lysed human and murine targets in chromium release and dye exclusion assays. Defensin-mediated tumor cell lysis was concentration-dependent, inhibited by serum, and dependent on temperature-sensitive events. Lysis was first detected by three hours of incubation and it reached a plateau between eight and 14 hours. In vitro exposure of murine teratocarcinoma cells to HNP 1-3 abrogated their oncogenicity in vivo. Nonmalignant target cells were also susceptible to defensin-mediated lysis. Four rabbit granulocyte defensins exerted marked (NP-1, NP-2) or moderate (NP-3a, NP-3b) cytotoxic activity, whereas defensin NP-5 was not cytotoxic. When tumor cells were incubated with human defensins in combination with hydrogen peroxide, synergistic cytotoxicity was detected. As defensins are released from granulocytes by various stimuli, their release could contribute to extracellular cytotoxicity which is independent of reactive oxygen intermediates.
我们检测了防御素（一种富含半胱氨酸的阳离子肽，在人和兔的粒细胞胞质颗粒中含量丰富）对各种肿瘤靶标的活性。三种人防御素HNP-1、HNP-2和HNP-3，在铬释放试验和染料排除试验中可裂解人和鼠的靶标。防御素介导的肿瘤细胞裂解呈浓度依赖性，受血清抑制，且依赖于温度敏感事件。孵育三小时后首次检测到裂解，八至十四小时达到平台期。将鼠畸胎瘤细胞在体外暴露于HNP 1-3可消除其在体内的致癌性。非恶性靶细胞也易受防御素介导的裂解作用影响。四种兔粒细胞防御素表现出显著（NP-1、NP-2）或中等（NP-3a、NP-3b）的细胞毒性活性，而防御素NP-5没有细胞毒性。当肿瘤细胞与人防御素及过氧化氢共同孵育时，可检测到协同细胞毒性。由于防御素可通过各种刺激从粒细胞中释放，其释放可能导致不依赖于活性氧中间体的细胞外细胞毒性。
