Document Detail


Extended blood half-life of monomethoxypolyethylene glycol-conjugated hen lysozyme is a key parameter controlling immunological tolerogenicity.
MedLine Citation:
PMID:  10442096     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
T So; H O Ito; M Hirata; T Ueda; T Imoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cellular and molecular life sciences : CMLS     Volume:  55     ISSN:  1420-682X     ISO Abbreviation:  Cell. Mol. Life Sci.     Publication Date:  1999 Jul 
Date Detail:
Created Date:  1999-09-07     Completed Date:  1999-09-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9705402     Medline TA:  Cell Mol Life Sci     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  1187-94     Citation Subset:  IM    
Affiliation:
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Half-Life
Immune Tolerance / drug effects*
Immunization
Immunization Schedule
Immunization, Secondary
Lymphocyte Activation
Mice
Mice, Inbred BALB C
Muramidase / metabolism,  pharmacokinetics*
Polyethylene Glycols / metabolism,  pharmacokinetics*
T-Lymphocyte Subsets / immunology*
Chemical
Reg. No./Substance:
0/Polyethylene Glycols; 0/monomethoxypolyethylene glycol--conjugated hen lysozyme; EC 3.2.1.17/Muramidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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