The antitumor drug streptozotocin (STZ) is commonly used as a diabetogenic compound in animal models. At relatively low doses, STZ-induced β cell destruction is associated with Th1-driven type 1 immune reactions, including macrophages (MΦ) and IFN-γ-producing CD8+ T cells. STZ induces similar Th1-dependent effects in the popliteal lymph node assay (PLNA), and because this assay allows straightforward examination of early immunostimulating processes, the PLNA was used to further examine the importance of MΦ and structural properties of STZ in relation to the induction of type 1 immune responses. Results show that elimination of MΦ with clodronate-containing liposomes prior to exposure to STZ prevents the occurrence of some (CD8+ T cell activation, IFN-γ production, and tissue destruction) but not all (IgG2a formation) type 1 immune responses. It appeared that stimulation of MΦ depends on 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 immune responses. Present results support the idea that MΦ activation is indispensable for the STZ-induced tissue destructive type 1 responses and that various STZ-induced type 1 immune responses are differently regulated.
|Tijdschrift||Chemical Research in Toxicology|
|Nummer van het tijdschrift||5|
|Status||Gepubliceerd - mei 2005|