octaarginine and lactacystin
octaarginine has been researched along with lactacystin* in 2 studies
Other Studies
2 other study(ies) available for octaarginine and lactacystin
Article | Year |
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Enhanced antigen presentation and CTL activity by transduction of mature rather than immature dendritic cells with octaarginine-modified liposomes.
To improve uptake and cross-presentation of exogenous antigens (Ag) by dendritic cells (DCs), octaarginine-modified liposomes (R8-Lip) were used as a novel strategy for protein-Ag transduction. Immature DCs endocytose macromolecules efficiently. While mature DCs lose their ability to capture Ag, but have an increased capacity for T-cell activation. Thus Ag-transduction has been performed mostly in immature DCs. In the present study, R8-Lip were efficiently taken up by both immature and mature DCs. DCs transduced after maturation were highly efficient at cross-presentation of Ag and induced higher cytotoxic T-lymphocytes (CTL) activity than were DCs transduced before maturation. The mechanism of Ag presentation involved the escape of R8-Lip from endosomes to cytosol, which require the acidic environment. The Ag released was then processed by a proteasome-dependent pathway. This novel transduction approach is clinically applicable, easy to perform, and has more practical advantages than current protein transduction methods. Topics: Acetylcysteine; Animals; Antigen Presentation; Cysteine Proteinase Inhibitors; Dendritic Cells; Endocytosis; Histocompatibility Antigens Class I; Immunodominant Epitopes; Liposomes; Mice; Mice, Inbred C57BL; Oligopeptides; T-Lymphocytes, Cytotoxic | 2009 |
Efficient MHC class I presentation by controlled intracellular trafficking of antigens in octaarginine-modified liposomes.
Recently, much attention has been paid to cell-penetrating peptides (CPPs) as an antigen-delivery tool for presentation through the major histocompatibility complex class I (MHC-I) pathway. However, escape of CPPs from the endosome is inefficient and therefore a bottleneck for antigen delivery. Previously, we showed the importance of topological control of octaarginine (R8) peptides on the liposome surface for regulating cellular uptake as well as intracellular trafficking, especially endosomal escape. In this study, we hypothesized that efficient MHC-I presentation could be achieved by controlled intracellular trafficking of antigen encapsulated in R8-modified liposomes (R8-Lip). The mechanism of uptake of both R8-Lip and cationic liposomes was shown to be by macropinocytosis in dendritic cells. However, confocal laser scanning microscopy (CLSM) revealed that R8-Lip are able to release significantly more antigen to the cytosol than are cationic liposomes. Processing of the antigens delivered by R8-Lip was shown to be proteasome-dependent, which is consistent with selective antigen presentation by R8-Lip via MHC-I. According to antigen-presentation analysis, R8-Lip can induce significantly higher MHC-I presentation at lower doses than either soluble ovalbumin (OVA) or OVA in pH-sensitive or cationic liposomes. Moreover, R8-Lip showed an efficient antitumor effect in vivo. Therefore, R8-Lip is a promising new carrier for MHC-I-specific antigen presentation. Topics: Acetylcysteine; Amiloride; Animals; Antigen Presentation; Bone Marrow Cells; Cell Line, Tumor; Cells, Cultured; Dendritic Cells; Flow Cytometry; Histocompatibility Antigens Class I; Intracellular Space; Liposomes; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Neoplasms, Experimental; Nocodazole; Oligopeptides; Tumor Burden | 2008 |