Norspermidine inhibits LPS-induced immunoglobulin production in an FCS-independent mechanism different from spermidine and spermine.
The immunosuppressive effects of several polyamines were compared. The triamines (norspermidine (NSPD) and spermidine (SPD] and the tetramines (norspermine (NSPM) and spermine (SPM] but not the diamines (1,3-diaminopropane and putrescine) inhibited IgM production from murine splenocytes stimulated with LPS. The estimated IC50 of NSPD was 2.29 x 10(-7) M. The inhibitory effect of NSPD on IgM production was associated with the inhibition of cell growth, because DNA and RNA syntheses measured by 3H-TdR and 3H-UR incorporation were also similarly reduced. Interestingly, the inhibitory effects of NSPD were over ten times greater than those of SPD in spite of the fact that their difference in chemical structure is only one carbon chain. In a FCS-free medium NSPD retained its suppressive activities on LPS-induced IgM production, but the other polyamines were remarkably weakened in their activities. These immunosuppressive effects of NSPD were prevented by adding substances of the intracellular polyamine metabolism, putrescine, SPD or SPM. These findings suggest that NSPD inhibits B cell growth and differentiation by interfering with the polyamine metabolism pathway.
Komori
T
T
Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd, Shizuoka, Japan.
Ohsugi
Y
Y
D000818:Animals; D003470:Culture Media; D004247:DNA / Q000096:biosynthesis; D005260:Female; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D007166:Immunosuppressive Agents; D066298:In Vitro Techniques; D051379:Mice; D011700:Putrescine / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D013095:Spermidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology
D003470:Culture Media; D007075:Immunoglobulin M; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D013096:Spermine; C006760:norspermidine; D012313:RNA; D004247:DNA; D013095:Spermidine; D011700:Putrescine