Antúnez Lorena R, Livingston Andrea, Berkland Cory, Dhar Prajnaparamita
Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas 66047, United States.
Department of Chemical and Petroleum Engineering, University of Kansas , Lawrence, Kansas 66045, United States.
Mol Pharm. 2016 May 2;13(5):1731-7. doi: 10.1021/acs.molpharmaceut.6b00111. Epub 2016 Mar 30.
Most vaccines contain aluminum adjuvants; however, their exact mechanism of action remains unclear. A novel mechanism by Shi and colleagues proposes aluminum adjuvants may enhance immune activation by binding and reorganizing lipids that are key components of lipid rafts. To better understand the specificity of interaction between aluminum adjuvants and the cell membrane lipids, we present a biophysical study of lipid domain clustering in simple model phospholipid monolayers containing dipalmitoyl-phosphatidylcholine (DPPC) and dioleoyl-phosphatidylcholine (DOPC) exposed to two aluminum adjuvants, Alhydrogel and Adju-Phos. Surface pressure measurements and fluorescence microscopy images verified aluminum adjuvant-induced increase in lipid domain size, even in the key lipid raft components. Additionally, adjuvant induced lipid clustering differed based on the physicochemical properties of the adjuvants. Alhydrogel appeared to reduce monolayer compressibility and insert into the monolayer, while Adju-Phos induced more significant changes in domain size, without compromising the integrity of the monolayer. The Alhydrogel and Adju-Phos-mediated reorganization of phospholipid domains reported here supports the new mechanistic paradigm proposed by Shi and co-workers, and further suggests that lipid clustering is induced even in simple phospholipid membranes. The results present the basis for future exploration into lipid-mediated mechanisms of action for adjuvants.
大多数疫苗都含有铝佐剂；然而，其确切作用机制仍不清楚。施及其同事提出了一种新机制，即铝佐剂可能通过结合和重组作为脂筏关键成分的脂质来增强免疫激活。为了更好地理解铝佐剂与细胞膜脂质之间相互作用的特异性，我们对含有二棕榈酰磷脂酰胆碱（DPPC）和二油酰磷脂酰胆碱（DOPC）的简单模型磷脂单层中脂质结构域聚集进行了生物物理研究，该单层暴露于两种铝佐剂，即氢氧化铝凝胶和磷酸铝佐剂。表面压力测量和荧光显微镜图像证实了铝佐剂可导致脂质结构域大小增加，即使在关键的脂筏成分中也是如此。此外，佐剂诱导的脂质聚集因佐剂的物理化学性质而异。氢氧化铝凝胶似乎降低了单层的可压缩性并插入到单层中，而磷酸铝佐剂诱导的结构域大小变化更为显著，同时又不损害单层的完整性。本文报道的氢氧化铝凝胶和磷酸铝佐剂介导的磷脂结构域重组支持了施及其同事提出的新机制范式，并进一步表明即使在简单的磷脂膜中也会诱导脂质聚集。这些结果为未来探索佐剂的脂质介导作用机制奠定了基础。
