Modulating the actions of NK cell-mediated cytotoxicity using lipid-PEG (n) and inhibitory receptor-specific antagonistic peptide conjugates.
Regulating the cell surface modulates the actions of the biological cell response, derives practical applications, and is of scientific interest. On the basis of our previous study using dioleylphosphatidylethanolamine poly(ethylene glycol) with multiple units of ethyleneoxide (DOPE-PEG (n)), we demonstrated the potency of DOPE-PEG (80) as a cell surface modulator. We prepared conjugates of DOPE-PEG (80) and two antagonistic peptides (C1, SGGGCLFNLPWLCG; C26, SGGGCPFSFLPWCG), specifically designed for the inhibitory receptor of natural killer (NK) cells. We confirmed that NK cells exhibited cytotoxicity against DOPE-PEG (80)-peptides-incorporated target cells. We further investigated whether the DOPE-PEG (80)-peptides could affect the cytotoxicity of NK cells in a concentration-dependent manner. C1 peptide showed down-regulation of cytotoxicity at higher concentration, whereas C26 peptide exhibited the saturated cytotoxicity of NK cells at the same concentration. These results suggest that DOPE-PEG (80) can achieve the role of a cell surface modulator without inhibiting the action of conjugated molecules, despite their relatively small size.
Chung
Hyeyoung A
HA
Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 1-3-7 Hongo, Bunkyo, Tokyo.
Tajima
Kyoko
K
Kato
Koichi
K
Matsumoto
Naoki
N
Yamamoto
Kazuo
K
Nagamune
Teruyuki
T
D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004306:Dose-Response Relationship, Immunologic; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000276:immunology; D011092:Polyethylene Glycols; D055630:Receptors, NK Cell Lectin-Like
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D000950:Antigens, Ly; D037181:Lectins, C-Type; D008055:Lipids; D010455:Peptides; D010714:Phosphatidylethanolamines; D055630:Receptors, NK Cell Lectin-Like; D011092:Polyethylene Glycols