Extended blood half-life of monomethoxypolyethylene glycol-conjugated hen lysozyme is a key parameter controlling immunological tolerogenicity.
The blood half-life of a protein is prolonged by conjugating a protein with a linear amphiphilic polymer, monomethoxypolyethylene glycol (mPEG). The conjugation gives a protein immunotolerogenicity; hence, it is likely that the long half-life is crucial for the tolerogenicity. We prepared a tolerogenic mPEG conjugate of hen egg lysozyme (mPEG1.5-HEL), which is conjugated 1.5-fold the molecular weight of mPEG against that of HEL, and evaluated the relationship between in vivo stability and the tolerogenicity. mPEG1.5-HEL retained immunogenicity to prime HEL-specific T cell and antibody responses and had a long blood half-life, more than 27 times that of native HEL. The tolerant state was maintained as long as mPEG1.5-HEL was detected in sera. With a decrease in the blood mPEG1.5-HEL level, the tolerant state returned gradually to the responsive state; however, reinjection of mPEG1.5-HEL again restored the tolerance. Thus, the extended blood half-life of HEL by mPEG conjugation is probably vital for establishing and maintaining the tolerant states.
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Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Ito
H O
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Hirata
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Ueda
T
T
Imoto
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D000818:Animals; D006207:Half-Life; D007108:Immune Tolerance / Q000187:drug effects*; D007114:Immunization; D007115:Immunization Schedule; D007117:Immunization, Secondary; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009113:Muramidase / Q000378:metabolism / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000378:metabolism / Q000493:pharmacokinetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
C120891:monomethoxypolyethylene glycol--conjugated hen lysozyme; D011092:Polyethylene Glycols; D009113:Muramidase