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NITRIC OXIDE PRODUCTION IN THE
CULTURE OF MONONUCLEAR LEUCOCYTES MODULATED BY SOLUBLE PRODUCTS
OF TUMOR CELLS
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ABSTRACT
Cells of the monocyte/macrophage lineage are capable of efficient killing of human nucleated tumor cells and this activity represents an important mechanism of host anti-tumor defense. Our previous investigation showed that in cancer patients, tumor-associated macrophages displayed a decreased capacity to produce and/or release nitric oxide. Therefore, we sought to investigate whether a tumor derived/induced products were responsible for this alteration.
Mononuclear cells used in this study were isolated with a density gradient. Isolated mononuclears were treated for 24h with different concentrations (dilutions 1:10, 1:102, 1:103, 1:104) of plasma, ascitic fluid and crude supernatants from short-term cultures of tumor cells obtained from a patient with peritoneal carcinomatosis, and then, nitric oxide production was measured.
It was found that, only the highest tested plasma and ascitic fluid concentrations caused marked stimulation of nitrix oxide production, whereas this effect disappeared in the presence of lower dose. In contrast, supernatants at low concentration suppressed nitric oxide production. Other concentrations have low stimulatory activity.
Generally, our results suggest that tumor products have potential to promote peripheral mononuclear suppressor activity by increasing systemic nitric oxide production and concurrently down-regulating the local production of these citotoxic molecules.
Keywords: nitric oxide, mononuclear leucocytes, tumor cells products
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