RESUMEN
A role for nitric oxide (NO) in the regulation of blood leukocyte numbers was examined in BALB/c mice by employing the NO synthase inhibitor NG-nitro L-arginine methyl ester (L-NAME). Treatment of animals with a single dose of 50 mg/kg body wt caused a dramatic increase in the number of circulating neutrophils and a moderate decrease in the number of circulating lymphocytes. These effects were partially reversed by the simultaneous inoculation of L-arginine (250 mg/kg body wt.) but not by D-arginine. A second NO synthase inhibitor, NG-nitro L-arginine, induced changes comparable to those elicited by L-NAME. Because catecholamines and glucocorticoids are well-known modulators of blood leukocyte counts, experiments were carried out in adrenalectomized mice. It was found that adrenalectomy did not modify the increase in the number of circulating neutrophils induced by L-NAME but completely prevented the decrease of circulating lymphocytes. Taken together, these findings support the hypothesis that NO plays an important role in the regulation of the peripheral blood number of neutrophils and lymphocytes, and that this function involves, in each case, the participation of different mechanisms.
Asunto(s)
Linfocitos/citología , Óxido Nítrico/fisiología , Animales , Arginina/análogos & derivados , Arginina/farmacología , Inhibidores Enzimáticos/farmacología , Recuento de Leucocitos/efectos de los fármacos , Linfocitos/efectos de los fármacos , Linfopenia/sangre , Linfopenia/inducido químicamente , Masculino , Ratones , Ratones Endogámicos BALB C , NG-Nitroarginina Metil Éster , Neutropenia/sangre , Neutropenia/inducido químicamente , Neutrófilos/citología , Neutrófilos/efectos de los fármacos , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico Sintasa/antagonistas & inhibidores , Nitroarginina , EstereoisomerismoRESUMEN
The M3 mammary tumor was transplantable in syngeneic BALB/c mice, and metastasized spontaneously into the lungs. When primary tumors were resected in early stages of evolution (10 days), the number of mice with lung metastasis decreased. When specific soluble tumor extracts, tumor cell culture supernatant or formalinized tumor cells were inoculated 2 and 4 days after surgery, an enhancement of lung metastasis was observed. When splenectomy was performed at the time of tumor resection, this enhancement was abrogated. These results suggest that tumor plasma cell membranes or the products released by them play an important role in dormant metastases growth, but only in the presence of the spleen, suggesting its involvement in the mechanism of the metastatic process.