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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
1999-5-27
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pubmed:abstractText |
The introduction of reactive thiol groups in recombinant human tumor necrosis factor (TNF) alpha (rhTNF-alpha) by the reagent succinimidyl-S-acetylthioacetate resulted in the formation of a chemically stabilized rhTNF-alpha trimer (rhTNFalpha-AT; as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis). rhTNFalpha-AT showed a substantially enhanced protective efficacy against the development of experimental murine cerebral malaria (ECM) after intravenous injection compared to the protective efficacy of nonmodified rhTNF-alpha. Administration of thiolated rhTNF-alpha with protected thiol groups (rhTNFalpha-ATA; no stabilized trimers in vitro) exhibited the same protective efficacy against ECM, while in vitro bioactivity was reduced. Parasitemia was significantly suppressed in rhTNF-treated mice that were protected against ECM but not in treated mice that developed ECM. Protection against ECM was not related to increased concentrations in plasma of soluble TNF receptor 1 and 2 directly after injection or at the moment of development of ECM in nontreated mice. The results indicate that thiolation of rhTNF-alpha leads to the formation of stable trimers with increased potential in vivo.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10223910-1103152,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10223910-1331108,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10223910-1437278,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10223910-1485495,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/10223910-1849278,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/10223910-2056127,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/10223910-2922050,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10223910-3034874,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/10223910-8867667,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10223910-9458469
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0066-4804
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1027-33
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10223910-Animals,
pubmed-meshheading:10223910-Humans,
pubmed-meshheading:10223910-Injections, Intravenous,
pubmed-meshheading:10223910-Malaria, Cerebral,
pubmed-meshheading:10223910-Mice,
pubmed-meshheading:10223910-Plasmodium berghei,
pubmed-meshheading:10223910-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:10223910-Recombinant Proteins,
pubmed-meshheading:10223910-Succinimides,
pubmed-meshheading:10223910-Sulfhydryl Reagents,
pubmed-meshheading:10223910-Sulfides,
pubmed-meshheading:10223910-Tumor Necrosis Factor-alpha
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pubmed:year |
1999
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pubmed:articleTitle |
Thiolated recombinant human tumor necrosis factor-alpha protects against Plasmodium berghei K173-induced experimental cerebral malaria in mice.
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pubmed:affiliation |
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3508 TB Utrecht, The Netherlands.
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pubmed:publicationType |
Journal Article
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