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.
Tokyo University of Pharmacy and Life Sciences, Horinouchi, Hachioji, Tokyo, Japan.
Katsuki
K
Takano
Kaori
K
Sato
Yoichi
Y
Negishi
Yukihiko
Y
Aramaki
D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000588:Amines / Q000737:chemistry; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D015638:Cytochalasin D / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D051745:Protein Kinase C-delta / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011509:Proteoglycans / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D000199:Actins; D000588:Amines; D008081:Liposomes; D011509:Proteoglycans; D017382:Reactive Oxygen Species; D015638:Cytochalasin D; D051745:Protein Kinase C-delta; C009317:stearylamine