Enhancement of liposomal model membrane immunogenicity by incorporation of lipid A.
Enhancement of liposomal model membrane immunogenicity by incorporation of lipid A.
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通过掺入脂质 A 增强脂质体模型膜的免疫原性。
DOI：
10.4049/jimmunol.119.6.1868
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发表时间：
1977
影响因子：
4.4
通讯作者：
S. Kinsky
中科院分区：
文献类型：
--
作者：
G. F. Dancey;T. Yasuda;S. Kinsky
将脂质A掺入鞘磷脂-胆固醇-磷酸二鲸蜡酯脂质体中可刺激AKR小鼠（和其他近交系）对模型膜的体液应答，模型膜也用合成的两亲性抗原二硝基苯基-ε-氨基己酰基磷脂酰乙醇胺（DNP-Cap-PE）致敏。用含有不同量的DNP-Cap-PE的脂质体观察到这种效果，并且其大小取决于掺入的脂质A的量。在用DNP-Cap-PE致敏的脂质体（缺乏脂质A）和用脂质A制备的脂质体（缺乏DNP-Cap-PE）的混合物免疫的小鼠的脾脏中，直接抗DNP空斑形成细胞（PFC）的频率没有显著增加。因此，脂质A对脂质体免疫原性的增强取决于其在含有DNP-Cap-PE的相同双层中的存在。这些结果进一步表明，脂质A与抗原决定簇的共价连接不是获得增加的半抗原特异性应答所必需的。
三条证据支持以下结论：刺激可归因于脂质A对骨髓源性（B）淋巴细胞的已知促有丝分裂作用。1)在AKR小鼠中，加入碱处理的脂质A（非促有丝分裂性）不会增强DNP-Cap-PE致敏脂质体的免疫原性。2)相反，脂质A掺入对C3 H/HeJ小鼠中的抗DNP PFC产生没有影响，C3 H/HeJ小鼠是一种具有对该有丝分裂原无反应的B细胞的品系。3)相比之下，脂质A确实增加了胸腺衍生（T）淋巴细胞缺乏的裸鼠或胸腺切除小鼠对DNP-Cap-PE致敏脂质体的反应。
现有的数据表明，脂质体免疫原性的调制脂质A可能是一种有效的方法，用于增强抗体形成对脂质抗原。
Incorporation of lipid A into sphingomyelin-cholesterol-dicetylphosphate liposomes stimulates the humoral response of AKR mice (and other inbred strains) to model membranes that are also sensitized with the synthetic amphipathic antigen, dinitrophenyl-ε-aminocaproylphosphatidylethanolamine (DNP-Cap-PE). This effect is observed with liposomes containing varying amounts of DNP-Cap-PE and the magnitude depends on the quantity of lipid A that is incorporated. No significant increase in the frequency of direct anti-DNP plaque-forming cells (PFC) is apparent in the spleens of mice immunized with a mixture of DNP-Cap-PE sensitized liposomes (lacking lipid A) and liposomes prepared with lipid A (lacking DNP-Cap-PE). Thus, enhancement of liposomal immunogenicity by lipid A is contingent on its presence in the same bilayers that contain DNP-Cap-PE. These results further indicate that covalent attachment of lipid A to an antigenic determinant is not required to obtain an increased hapten-specific response.
Three lines of evidence support the conclusion that stimulation can be attributed to the known mitogenic effect of lipid A on bone marrow-derived (B) lymphocytes. 1) Incorporation of alkali-treated lipid A, which is nonmitogenic, does not enhance the immunogenicity of DNP-Cap-PE sensitized liposomes in AKR mice. 2) Conversely, lipid A incorporation had no effect on anti-DNP PFC production in C3H/HeJ mice, a strain possessing B cells that are not responsive to this mitogen. 3) In contrast, lipid A did increase the response to DNP-Cap-PE sensitized liposomes in either nude or thymectomized mice that are deficient in thymus-derived (T) lymphocytes.
The available data suggest that modulation of liposomal immunogenicity by lipid A may be an effective method for enhancing antibody formation against lipid antigens.