Gorelik E, Wiltrout R H, Brunda M J, Bere W E, Herberman R B
Clin Exp Metastasis. 1985 Apr-Jun;3(2):111-23. doi: 10.1007/BF01758960.
The effect of thioglycollate-elicited macrophages (TG-M phi) on natural killer (NK)-cell activity and metastases formation in mice was investigated. Intravenously (i.v.) inoculated TG-M phi inhibited spleen NK activity of normal mice and abrogated polyinosinic: polycytidylic (poly I:C) induced augmentation of NK cell function. TG-M phi also inhibited the clearance of i.v.-injected radiolabeled B16 melanoma cells from the lungs of normal or poly I:C stimulated mice. Formation of experimental B16 melanoma metastases was dramatically increased in mice pretreated with TG-M phi. Administration of TG-M phi increased metastasis formation to a greater extent than anti-asialo GM1 serum, while anti-asGM1 serum was more efficient than TG-M phi in depressing spleen NK cell activity. When mice with low NK reactivity (beige mice or mice treated with anti-asialo GM1 serum) were inoculated with TG-M phi, there was a substantial additive augmenting effect on metastasis formation in the lungs. Treatment with poly I:C elevated NK-cell activity and had profound antimetastatic effects in normal but not in TG-M phi pretreated mice. The metastasis augmenting effect of TG-M phi was fully expressed in poly I:C-treated mice as well as in athymic nude mice. Inoculation of proteose peptone-elicited macrophages (PM phi), unlike TG-M phi, did not depress NK activity or augment metastasis formation in normal or poly I:C-treated mice. However, since the inhibition of NK activity in TG-M phi-treated mice was relatively weak, and a substantial additional increase in metastases was observed in NK-depressed mice after transfusion of TG-M phi, it seems unlikely that the TG-M phi-induced inhibition of NK reactivity is entirely responsible for the augmented formation of metastases. Further studies revealed that i.v. inoculation of TG-M phi, but not PM phi, induced intravascular inflammatory reactions, and damage to endothelial cells and basement membrane of the lung vasculature. These reactions may contribute to increased tumor cell extravasation and metastasis formation in mice pretreated with TG-M phi.
研究了巯基乙酸盐诱导的巨噬细胞（TG-M phi）对小鼠自然杀伤（NK）细胞活性及转移形成的影响。静脉注射接种的TG-M phi可抑制正常小鼠脾脏NK活性，并消除聚肌苷酸：聚胞苷酸（poly I:C）诱导的NK细胞功能增强。TG-M phi还抑制正常或经poly I:C刺激的小鼠肺部对静脉注射放射性标记的B16黑色素瘤细胞的清除。用TG-M phi预处理的小鼠中，实验性B16黑色素瘤转移的形成显著增加。与抗唾液酸GM1血清相比，TG-M phi给药对转移形成的增加程度更大，而抗唾液酸GM1血清在抑制脾脏NK细胞活性方面比TG-M phi更有效。当低NK反应性的小鼠（米色小鼠或用抗唾液酸GM1血清处理的小鼠）接种TG-M phi时，对肺部转移形成有显著的相加增强作用。用poly I:C处理可提高NK细胞活性，并在正常小鼠而非经TG-M phi预处理的小鼠中具有显著的抗转移作用。TG-M phi的转移增强作用在经poly I:C处理的小鼠以及无胸腺裸鼠中均充分表现出来。与TG-M phi不同，接种蛋白胨诱导的巨噬细胞（PM phi）不会抑制正常或经poly I:C处理的小鼠的NK活性或增强转移形成。然而，由于TG-M phi处理的小鼠中NK活性的抑制相对较弱，并且在输注TG-M phi后NK抑制的小鼠中观察到转移显著额外增加，因此TG-M phi诱导的NK反应性抑制似乎不太可能完全是转移形成增加的原因。进一步研究表明，静脉注射接种TG-M phi而非PM phi会诱导血管内炎症反应，并损伤肺血管的内皮细胞和基底膜。这些反应可能有助于TG-M phi预处理的小鼠中肿瘤细胞外渗和转移形成增加。
