Boggs J M, Chang N H, Goundalkar A
Department of Biochemistry, Hospital for Sick Children, Toronto, Ontario, Canada.
Antimicrob Agents Chemother. 1991 May;35(5):879-85. doi: 10.1128/AAC.35.5.879.
The effects of free amphotericin B (as Fungizone) and amphotericin B (AMB) incorporated into liposomes on the proliferation of lymphocytes were determined. Freshly obtained guinea pig and rat antigen-specific lymphocytes were compared with rat T-lymphocyte cell lines cultured for a long period of time. Incorporation of AMB into multilayered vesicles significantly reduced its effect relative to that of Fungizone on cultured T-cell lines, as reported by others for mammalian cells. In contrast, the effects on freshly obtained antigen-specific lymphocytes were different. Fungizone inhibited proliferation of antigen-specific lymph node cells freshly obtained from immunized guinea pigs at fungicidal concentrations, and incorporation into multilayered lipid vesicles did not have much of a protective effect. Higher concentrations of Fungizone were required to inhibit proliferation of fresh rat lymph node cells, but incorporation into multilayered lipid vesicles still did not have much of a protective effect. Some T lymphocytes in the peripheral circulation of guinea pigs and in the lymph nodes of rats were more resistant to liposomal AMB than another more sensitive T-lymphocyte population was. Proliferation of lymphocytes in response to mitogens was inhibited less than that in response to specific antigen was. Thus, sensitivity to AMB depended on the species, the strength of the stimulus used to activate the lymphocytes, and on some other property of the lymphocytes, possibly their state of differentiation. Regardless of the reason for the difference in effects on freshly obtained lymph node lymphocytes and cultured line cells, the former may be more relevant to effects in vivo and should be considered in a complete evaluation of the in vivo toxicity of these forms of the drug. Incorporation into sonicated unilamellar vesicles had more of a protective effect, while equimolar drug-lipid complexes had even more of a protective effect. These forms of AMB might have less of an immunosuppressive potential than multilayered vesicles containing low amounts of AMB do.
测定了游离两性霉素B（如两性霉素B注射剂）和脂质体包裹的两性霉素B（AMB）对淋巴细胞增殖的影响。将新获得的豚鼠和大鼠抗原特异性淋巴细胞与长期培养的大鼠T淋巴细胞系进行比较。正如其他人对哺乳动物细胞所报道的那样，相对于两性霉素B注射剂，将AMB包裹于多层囊泡中可显著降低其对培养的T细胞系的作用。相比之下，对新获得的抗原特异性淋巴细胞的作用则有所不同。两性霉素B注射剂在杀菌浓度下可抑制从免疫豚鼠新鲜获得的抗原特异性淋巴结细胞的增殖，而包裹于多层脂质囊泡中则没有太大的保护作用。抑制新鲜大鼠淋巴结细胞的增殖需要更高浓度的两性霉素B注射剂，但包裹于多层脂质囊泡中仍没有太大的保护作用。豚鼠外周循环中的一些T淋巴细胞以及大鼠淋巴结中的一些T淋巴细胞比另一些更敏感的T淋巴细胞群体对脂质体AMB更具抗性。与对特异性抗原的反应相比，有丝分裂原刺激引起的淋巴细胞增殖受到的抑制较小。因此，对AMB的敏感性取决于物种、用于激活淋巴细胞的刺激强度以及淋巴细胞的其他某些特性，可能是它们的分化状态。无论对新鲜获得的淋巴结淋巴细胞和培养系细胞的作用存在差异的原因是什么，前者可能与体内作用更相关，在全面评估这些药物形式的体内毒性时应予以考虑。包裹于超声处理的单层囊泡中具有更大的保护作用，而等摩尔的药物 - 脂质复合物具有甚至更大的保护作用。这些形式的AMB可能比含有少量AMB的多层囊泡具有更低的免疫抑制潜力。
