Immunological alterations induced by polyamine derivatives on murine splenocytes and human mononuclear cells.
Three polyamine derivatives assigned as bis-naphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd) and spermine (BNIPSpm) were studied to determine their effects on the proliferation of murine splenocytes and human peripheral blood mononuclear cells (PBMC) induced by the mitogens, Con A, LPS and PHA. All compounds showed a dose dependent inhibitory effect on mouse and human T cell proliferation induced by the mitogens, with BNIPPut exhibiting the most potent antiproliferative activity, followed by BNIPSpd and by BNIPSpm, respectively (Put > Spd > Spm), when considering human T cells. This suppressive activity also affects the capacity of mouse spleen cells to produce Th1 cytokines, namely IL-2 and INF-gamma after in vitro stimulation with Con A. The polyamine-induced inhibition also occurred in the case of LPS-stimulated B cells with a marked decrease of CD69 expression by these cells. Furthermore, the ability for these polyamine derivatives to induce apoptosis on Con A-stimulated splenocytes could be related to their antiproliferative activity.
Cordeiro-da-Silva
Anabela
A
Laboratório de Bioquímica, Faculdade de Farmácia da Universidade do Porto, Rua Anibal Cunha, 164, Oporto 4050, Portugal. cordeiro@mail.ff.up.pt
Tavares
Joana
J
Araújo
Natália
N
Cerqueira
Fátima
F
Tomás
Ana
A
Kong Thoo Lin
Paul
P
Ouaissi
Ali
A
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology*; D013095:Spermidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D037181:Lectins, C-Type; D015363:Quinolones; D013095:Spermidine; D000099192:CD69 Antigens; C439296:bisnaphthalimidopropylspermidine