Cationic liposomes suppress intracellular calcium ion concentration increase via inhibition of PI3 kinase pathway in mast cells

摘要

Abstract Cationic liposomes are commonly used as vectors to effectively introduce foreign genes (antisense DNA, plasmid DNA, siRNA, etc.) into target cells. Cationic liposomes are also known to affect cellular immunocompetences such as the mast cell function in allergic reactions. In particular, we previously showed that the cationic liposomes bound to the mast cell surface suppress the degranulation induced by cross-linking of high affinity IgE receptors in a time- and dose-dependent manner. This suppression is mediated by impairment of the sustained level of intracellular Ca 2+ concentration ([Ca 2+ ] i ) via inhibition of store-operated Ca 2+ entry (SOCE). Here we study the mechanism underlying an impaired [Ca 2+ ] i increase by cationic liposomes in mast cells. We show that cationic liposomes inhibit the phosphorylation of Akt and PI3 kinases but not Syk and LAT. As a consequence, SOCE is suppressed but Ca 2+ release from endoplasmic reticulum (ER) is not. Cationic liposomes inhibit the formation of STIM1 puncta, which is essential to SOCE by interacting with Orai1 following the Ca 2+ concentration decrease in the ER. These data suggest that cationic liposomes suppress SOCE by inhibiting the phosphorylation of PI3 and Akt kinases in mast cells. Graphical abstract Display Omitted Highlights ? Cationic liposomes bound to the mast cell surface suppress store-operated Ca 2+ entry. ? Cationic liposomes inhibit the phosphorylation of Akt and PI3 kinases. ? Cationic liposomes did not inhibit the phosphorylation Syk and LAT. ? Cationic liposomes inhibit the formation of STIM1 puncta.