Effects of lipid composition in cationic liposomes on suppression of mast cell activation

We previously showed that cationic liposomes composed of cholesteryl-3β-carboxyamidoethylene-N-hydroxyethylamine (OH-Chol) and 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) inhibited mast cell degranulation mediated by the cross-linking of high-affinity IgE receptors (FcεRI). In this study, we prepared three kinds of cationic liposomes composed of OH-Chol and DOPE in different ratios (0.28, 0.60, and 0.86 of OH-Chol in mol ratio, named as L-liposome, M-liposome, and H-liposome, respectively) and investigated their effects on mast cell activation. We found that mast cell degranulation evoked with antigen was inhibited by pretreatment with cationic liposomes in the composite ratio-dependent manner of OH-Chol and that the H-liposome showed the highest inhibitory effect on degranulation among three kinds of liposomes. Store-operated Ca²⁺ entry, phosphorylation of PI3K and Akt, and IL-4 secretion after antigen stimulation were reduced in dose-dependent manner of each liposome, but there were no differences between H-liposome and M-liposome. Meanwhile, microtubule acetylation, which is involved in the secretory granule transport, was significantly suppressed by H-liposome compared with M-liposome. These data suggested that the lipid composition in cationic liposomes themselves largely influenced the inhibition of mast cell activation as well as the efficiency of gene transfection.