Lymphocyte activation by liposome-trapped streptozotocin in murine popliteal lymph node (PLN) test.
The lymphoproliferative potential of liposome-trapped streptoztocin (STZ) was compared to the effect of saline-dissolved STZ injected locally into the foot pad of CD-1 mice. Popliteal lymph node (PLN) enlargement and early cell activation of lymphocyte subsets were monitored during the onset of STZ-induced autoimmune-like reaction. Injection of the optimal STZ dose, 0.5 mg/foot pad, markedly increased the absolute PLN cell number as well as specific T-helper (CD4+), T-suppressor/cytotoxic (CD8+), and B-(Ig+) cell subsets stained with fluorescent monoclonal antibodies. Furthermore, there was a marked increase in the number of large/activated CD4+ and CD8+ cells and subsets bearing specific markers of early activation. These included cells stained with fluorescein-conjugated monoclonal antibodies against interleukin-2 receptor (CD25+) and early activation marker (EAM+) (CD69+), and with fluorescein-conjugated peanut agglutinin (PNA+). Surprisingly, the injection of liposome-trapped STZ, at a 1/10 of the optimal dose only, induced a marked PLN enlargement comparable to the effect of optimal STZ dose. The effect of liposome-STZ could be dissociated from the non-drug-containing MLV-related lymphocyte activation. The data suggest several possible advantages from the introduction of chemicals by the liposome route and the subsequent PLN test for chemical-induced autoimmunity. Toxicological advantages could involve better control of chemical exposure, controlled exposure to the water-insoluble substances, drastic reduction of xenobiotic dose, a stronger, clear PLN response and possible elimination or at least restriction of false-negative results, due to the liposome adjuvancity. Overall, application of liposomes as an exposure route potentialized the STZ-induced early lymphocyte activation.
Krzystyniak
K
K
Départment des Sciences Biologiques, Université du Québec à Montréal, Canada.
Desjardins
R
R
Thérien
H M
HM
Banska
W
W
Tancrede
P
P
Descotes
J
J
D000818:Animals; D015551:Autoimmunity; D005260:Female; D008081:Liposomes / Q000008:administration & dosage*; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D013311:Streptozocin / Q000008:administration & dosage* / Q000494:pharmacology
D008081:Liposomes; D013311:Streptozocin