Sone S, Mutsuura S, Ogawara M, Tsubura E
J Immunol. 1984 Apr;132(4):2105-10.
Human monocytes harvested from healthy donors and separated by discontinuous gradient centrifugation and adherence were highly cytotoxic to allogeneic melanoma cells, but did not affect nontumorigenic cells, as measured by lysis of the cells. After 4 days incubation of these monocytes in medium, they showed little, if any, cytolytic activity. Hydrophilic muramyl dipeptide (MDP) or lipophilic muramyl tripeptide (MTP-PE) was encapsulated within multilamellar (MLV) liposomes composed of phosphatidylserine-phosphatidylcholine. The cultured monocytes were rendered tumoricidal by interaction for 24 hr with MDP or liposomes containing soluble MDP or lipophilic MTP-PE. Moreover, freshly isolated monocytes treated for 24 hr with liposomes containing MDP or MTP-PE remained tumoricidal during culture for up to 5 days. About 1,600-times lower concentration of MDP entrapped in liposomes than of free MDP in the medium was effective for rendering monocytes tumoricidal. Similarly, about 80-times lower concentration of MTP-PE in liposomes than of free MDP was effective for the activation of monocytes. It is concluded that MLV liposomes containing MDP or MTP-PE are far more efficient in potentiating the tumoricidal activity of human monocytes than unencapsulated, free MDP.
从健康供体采集的人类单核细胞，通过不连续梯度离心和贴壁分离后，对同种异体黑色素瘤细胞具有高度细胞毒性，但对非致瘤细胞没有影响，这通过细胞裂解来衡量。这些单核细胞在培养基中孵育4天后，几乎没有（如果有的话）细胞溶解活性。亲水性胞壁酰二肽（MDP）或亲脂性胞壁酰三肽（MTP-PE）被包裹在由磷脂酰丝氨酸-磷脂酰胆碱组成的多层脂质体（MLV）中。培养的单核细胞通过与MDP或含有可溶性MDP或亲脂性MTP-PE的脂质体相互作用24小时而具有杀肿瘤活性。此外，用含有MDP或MTP-PE的脂质体处理24小时的新鲜分离单核细胞在培养长达5天期间仍具有杀肿瘤活性。脂质体中包裹的MDP浓度比培养基中游离MDP浓度低约1600倍时，对使单核细胞具有杀肿瘤活性有效。同样，脂质体中MTP-PE浓度比游离MDP低约80倍时，对单核细胞的激活有效。得出的结论是，含有MDP或MTP-PE的MLV脂质体在增强人类单核细胞的杀肿瘤活性方面比未包裹的游离MDP效率高得多。
