Gorelik E, Wiltrout R H, Copeland D, Herberman R B
Cancer Immunol Immunother. 1985;19(1):35-42. doi: 10.1007/BF00199309.
We have studied the formation of experimental B16 melanoma metastases in the lungs of mice inoculated IV with tumoricidal or nontumoricidal peritoneal macrophages elicited by various agents. IV inoculation of peritoneal M phi elicited by Brewer's thioglycollate medium (TG-M phi) 1 day before the injection of B16 melanoma cells dramatically increased the number of metastatic foci in the lungs. NIH thioglycollate broth and proteose peptone each elicited a relatively low number of M phi, which were morphologically distinguishable from TG-M phi and did not influence the yield of B16 melanoma colonies in the lungs. Resident or C. pravum-elicited M phi also did not augment metastasis formation. TG-M phi became highly tumoricidal after IP stimulation with poly I:C. However, tumoricidal TG-M phi inoculated IV 1 day before IV inoculation of B16 melanoma cells did not have an antimetastatic effect. On the contrary, both tumoricidal and nontumoricidal TG-M phi augmented metastasis formation. Poly I:C treatment had a substantial antimetastatic effect in the normal mice, but not in mice with adoptively transferred TG-M phi. Histological analysis revealed that IV-inoculated TG-M phi (tumoricidal or nontumoricidal, either viable or disrupted) induced severe intravascular reaction in the lungs, but not in the liver or kidney. This reaction manifested in the aggregation of the various blood cells, preferentially neutrophils. These reactions were not observed after IV inoculation of PM phi or NIH TG-M phi. Intravascular inflammatory reactions induced by TG-M phi may be responsible for the augmentation of metastasis formation, partly by suppression of NK reactivity and mostly by the acceleration of the processes of tumor cell extravasation. These data may provide some insight into the failure to achieve systemic adoptive immunotherapy using activated peritoneal TG-M phi.
我们研究了用各种制剂诱导产生的具有杀肿瘤或无杀肿瘤作用的腹腔巨噬细胞经静脉注射接种到小鼠体内后，实验性B16黑色素瘤在小鼠肺部转移灶的形成情况。在注射B16黑色素瘤细胞前1天经静脉接种由布鲁尔硫代乙醇酸盐培养基诱导产生的腹腔巨噬细胞（TG-M phi），可显著增加肺部转移灶的数量。NIH硫代乙醇酸盐肉汤和蛋白胨各自诱导产生的巨噬细胞数量相对较少，在形态上与TG-M phi可区分，且不影响肺部B16黑色素瘤集落的产生。驻留或由短小棒状杆菌诱导产生的巨噬细胞也不会增强转移灶的形成。用聚肌胞苷酸（poly I:C）腹腔刺激后，TG-M phi具有高度杀肿瘤作用。然而，在经静脉接种B16黑色素瘤细胞前1天经静脉接种具有杀肿瘤作用的TG-M phi并没有抗转移作用。相反，具有杀肿瘤作用和无杀肿瘤作用的TG-M phi均增强了转移灶的形成。聚肌胞苷酸处理对正常小鼠有显著的抗转移作用，但对经TG-M phi过继转移的小鼠则无此作用。组织学分析显示，经静脉接种的TG-M phi（具有杀肿瘤或无杀肿瘤作用，无论存活或已裂解）在肺部诱导了严重的血管内反应，但在肝脏或肾脏中未观察到。这种反应表现为各种血细胞的聚集，以中性粒细胞为主。经静脉接种PM phi或NIH TG-M phi后未观察到这些反应。TG-M phi诱导的血管内炎症反应可能部分通过抑制自然杀伤细胞活性，主要通过加速肿瘤细胞外渗过程，导致转移灶形成增加。这些数据可能为使用活化的腹腔TG-M phi进行全身过继免疫治疗失败提供一些见解。
