Inducible nitric oxide synthase-mediated proliferation of a T lymphoma cell line.
Nitric oxide (NO)-derived from T lymphocytes in an autocrine fashion can modulate events in the cell. However, the exact role of NO on the control of lymphocyte growth is controversial since both stimulation and inhibition have been demonstrated. Nitric oxide synthase (NOS) activity in normal and tumor T lymphocyte proliferation was studied here. Resting normal T lymphocytes displayed low levels of NOS activity that were slightly increased upon mitogenic stimulation. In contrast, BW5147 T lymphoma cells displayed higher basal levels than normal T lymphocytes that were significantly augmented when induced to proliferate. This activity was slightly modified in the presence of the calcium chelator EGTA and was blocked by competitive and irreversible NOS inhibitors, as well as by selective blockers of iNOS. Furthermore, tumor but not normal cell proliferation was impaired by NOS and iNOS blockers, while a calcium blocker only affected normal cell growth. iNOS expression, both at the protein and at the mRNA levels, was demonstrated on growing BW5147 cells but not on arrested tumor or normal lymphocytes. The contribution of iNOS to sustained proliferation of tumor cells is discussed.
Barreiro Arcos
Maria Laura
ML
Centro de Estudios Farmacológicos y Botánicos (CEFYBO)-CONICET, Serrano 669 (1414), Buenos Aires, Argentina.
Gorelik
Gabriela
G
Klecha
Alicia
A
Goren
Nora
N
Cerquetti
Cristina
C
Cremaschi
Graciela A
GA
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002455:Cell Division; D045744:Cell Line, Tumor / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D008213:Lymphocyte Activation; D008223:Lymphoma; D008934:Mitogens / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
D002121:Calcium Channel Blockers; D002614:Chelating Agents; D008934:Mitogens; D009569:Nitric Oxide; D004533:Egtazic Acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II