Ferluga J, Asherson G L, Becker E L
Immunology. 1972 Oct;23(4):577-90.
Organophosphorus (OP) agents are irreversible inhibitors of OP sensitive esterases. Their effect on the cytotoxic killing of Cr-labelled mastocytoma cells by immune spleen cells was assessed by the release of Cr. OP fluoridates inhibited cytotoxic killing whether used as a pretreatment before the addition of the labelled target cells or as a concurrent treatment. The effect of pretreatment was time, temperature and concentration dependent and was abolished by hydrolysis. It occurred at concentrations which did not inhibit the incorporation of [C] leucine and uridine. It is tentatively suggested that the OP agents inhibited an activated esterase present in the spleen cell before the cytotoxic reaction. In contrast, phosphonates inhibited cytotoxic killing when used concurrently but had little effect as a pretreatment. The chemically more reactive -nitrophenyl phosphonates and the much less reactive phenyl phosphonates inhibited cytotoxic killing to a similar degree. It was concluded that the phosphonates did not inhibit activated esterase. The effect of phosphonates was virtually abolished by hydrolysis. However the effect of the -nitrophenyl phosphonates was increased by hydrolysis. This was due to the -nitrophenol formed. Cytochalasin B, which is known to interfere with cell movements, and -nitrophenol, both of which inhibited spleen cell migration from a capillary tube, inhibited cytotoxic killing when used concurrently. This inhibition was partly reversed by shaking. It is suggested that movements of the cell surface may be essential, in the absence of shaking, to provide the contact needed for cytotoxic killing.
有机磷（OP）制剂是OP敏感酯酶的不可逆抑制剂。通过铬的释放来评估它们对免疫脾细胞杀伤铬标记肥大细胞瘤细胞的细胞毒性作用。OP氟化物无论是在添加标记靶细胞之前用作预处理，还是作为同时处理，都能抑制细胞毒性杀伤。预处理的效果取决于时间、温度和浓度，并且会因水解而消除。这种情况发生在不抑制[C]亮氨酸和尿苷掺入的浓度下。初步认为，OP制剂在细胞毒性反应之前抑制了脾细胞中存在的一种活化酯酶。相比之下，膦酸盐在同时使用时会抑制细胞毒性杀伤，但作为预处理时作用很小。化学活性更高的对硝基苯基膦酸盐和活性低得多的苯基膦酸盐对细胞毒性杀伤的抑制程度相似。得出的结论是，膦酸盐不会抑制活化酯酶。膦酸盐的作用实际上会因水解而消除。然而，对硝基苯基膦酸盐的作用会因水解而增强。这是由于形成了对硝基苯酚。已知细胞松弛素B会干扰细胞运动，对硝基苯酚都会抑制脾细胞从毛细管中迁移，它们在同时使用时会抑制细胞毒性杀伤。通过摇晃，这种抑制作用会部分逆转。有人认为，在不摇晃的情况下，细胞表面的运动对于提供细胞毒性杀伤所需的接触可能至关重要。
