Involvement of actin cytoskeleton in macrophage apoptosis induced by cationic liposomes

We clarified whether actin cytoskeleton is involved in the macrophage apoptosis induced by cationic liposomes composed of stearylamine (SA-liposomes). Externalization of phosphatidylserine induced by SA-liposomes was suppressed by cytochalasin D, a specific inhibitor of polymerization of F-actin. Furthermore, activation of PKCδ and reactive oxygen species (ROS) generation, which could be involved in the macrophage apoptosis, were inhibited by cytochalasin D. Microscopical observation revealed the co-localization of 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled SA-liposomes and fluorescein-labeled phalloidin, which specifically binds to F-actin, and this co-localization was also inhibited by cytochalasin D. Co-localization of SA-liposomes and F-actin was also inhibited by the pre-treatment of cells with chondroitinase ABC. These findings could be the first observation concerning the contribution of the proteoglycan–actin cytoskeleton–ROS generation pathway to apoptosis induced by SA-liposomes in macrophages.

► Actin cytoskeleton is implicated in macrophage apoptosis induced by cationic liposomes.
► Actin cytoskeleton is considered to be linked to PKCδ activation and ROS generation induced by cationic liposomes.
► Proteoglycan–actin cytoskeleton–ROS generation pathway is involved in macrophage apoptosis induced by SA-liposomes.