The Reactive D-Glucopyranose Moiety of Streptozotocin Is Responsible for Activation of Macrophages and Subsequent Stimulation of CD8+ T Cells
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- 作者：Stefan Nierkens ; Rob Bleumink ; Marianne Bol ; Ine Hassing ; Nico van Rooijen ; and Raymond Pieters
- 刊名：Chemical Research in Toxicology
- 出版年：2005
- 出版时间：May 2005
- 年：2005
- 卷：18
- 期：5
- 页码：872 - 879
- 全文大小：218K
- 年卷期：v.18,no.5(May 2005)
- ISSN：1520-5010
文摘
The antitumor drug streptozotocin (STZ) is commonly used as a diabetogenic compound inanimal models. At relatively low doses, STZ-induced 
cell destruction is associated with Th1-driven type 1 immune reactions, including macrophages (M
) and IFN-
-producing CD8+ Tcells. STZ induces similar Th1-dependent effects in the popliteal lymph node assay (PLNA),and because this assay allows straightforward examination of early immunostimulatingprocesses, the PLNA was used to further examine the importance of M and structuralproperties of STZ in relation to the induction of type 1 immune responses. Results show thatelimination of M with clodronate-containing liposomes prior to exposure to STZ preventsthe occurrence of some (CD8+ T cell activation, IFN- production, and tissue destruction) butnot all (IgG2a formation) type 1 immune responses. It appeared that stimulation of M dependson the D-glucopyranose moiety of STZ, as well as on the intact reactive N-methyl-N-nitrosourea(MNU) moiety. However, the MNU moiety suffices to induce IgG2a formation. In addition,STZ-derived nitric oxide may have modulating effects on the elicitation of STZ-induced immuneresponses. Present results support the idea that M activation is indispensable for the STZ-induced tissue destructive type 1 responses and that various STZ-induced type 1 immuneresponses are differently regulated.
cell destruction is associated with Th1-driven type 1 immune reactions, including macrophages (M) and IFN--producing CD8+ Tcells. STZ induces similar Th1-dependent effects in the popliteal lymph node assay (PLNA),and because this assay allows straightforward examination of early immunostimulatingprocesses, the PLNA was used to further examine the importance of M and structuralproperties of STZ in relation to the induction of type 1 immune responses. Results show thatelimination of M with clodronate-containing liposomes prior to exposure to STZ preventsthe occurrence of some (CD8+ T cell activation, IFN- production, and tissue destruction) butnot all (IgG2a formation) type 1 immune responses. It appeared that stimulation of M dependson the D-glucopyranose moiety of STZ, as well as on the intact reactive N-methyl-N-nitrosourea(MNU) moiety. However, the MNU moiety suffices to induce IgG2a formation. In addition,STZ-derived nitric oxide may have modulating effects on the elicitation of STZ-induced immuneresponses. Present results support the idea that M activation is indispensable for the STZ-induced tissue destructive type 1 responses and that various STZ-induced type 1 immuneresponses are differently regulated.