Taylor D D, Black P H
J Natl Cancer Inst. 1985 Apr;74(4):859-67.
Shed plasma membrane-derived vesicles from metastatic variants of the murine B16 melanoma were examined for their ability to inhibit the induction of murine immune region-associated (Ia) antigen expression on macrophages, the initial step in the formation of an immune response. Membrane material that appears as a greater than 50 million-dalton fraction on column chromatography is found only in conditioned media from tumor cells and not in culture media from normal cells, such as murine 3T3 cells. Membrane vesicles from both metastatic variants B16-F1 (low lung colonizing) and B16-F10 (high lung colonizing) were taken up by macrophages; however, only membrane vesicles isolated from the B16-F10 cultures exhibited significant inhibitory activity for Ia induction. This inhibition appears to result from enhanced prostaglandin synthesis, since treatment with aspirin can reverse the membrane vesicle-induced inhibition. The inhibitory component(s) released into the media was demonstrated to be predominantly associated with membrane vesicles; however, the component(s) retained its activity after Triton X-100 treatment, indicating that the intact membrane vesicle was not necessary for the action of the inhibitory material. Treatments with heat (65 degrees C) and proteases (papain) indicated that the inhibitory component(s) is a heat-labile protein.
对源自小鼠B16黑色素瘤转移变体的脱落质膜衍生囊泡进行了检测，以评估其抑制巨噬细胞上鼠免疫区域相关（Ia）抗原表达诱导的能力，这是免疫反应形成的初始步骤。在柱色谱上表现为大于5000万道尔顿级分的膜材料仅在肿瘤细胞的条件培养基中发现，而在正常细胞（如小鼠3T3细胞）的培养基中未发现。来自转移变体B16-F1（低肺定植）和B16-F10（高肺定植）的膜囊泡均被巨噬细胞摄取；然而，只有从B16-F10培养物中分离出的膜囊泡对Ia诱导表现出显著的抑制活性。这种抑制似乎是由于前列腺素合成增强所致，因为用阿司匹林处理可以逆转膜囊泡诱导的抑制作用。释放到培养基中的抑制成分被证明主要与膜囊泡相关；然而，该成分在经Triton X-100处理后仍保留其活性，这表明完整的膜囊泡对于抑制物质的作用并非必需。加热（65℃）和蛋白酶（木瓜蛋白酶）处理表明，抑制成分是一种热不稳定蛋白。
