Cytotoxic activity of BCG-activated macrophages against L929 tumor cells is nitric oxide-dependent

Autor(es)

F.R.F. Nascimento ^[1] ; F. Ribeiro-Dias ^[2] ; M. Russo ^[3]

Afiliação do(s) autor(es)

^[1] Universidade de São Paulo

^[2] Universidade de São Paulo

^[3] Universidade de São Paulo

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 31, n. 12 1998-12-00.

Resumo

The tumoricidal activity of activated macrophages has been attributed largely to the release of tumor necrosis factor (TNF), or to the production of reactive oxygen or nitrogen intermediates. The L929 tumor cell line (a murine fibroblast-like cell) when treated with actinomycin D (ActD) has been used to measure TNF<FONT FACE="Symbol">a</FONT> cytotoxicity. In the present study, we determined the cytotoxic activity of BCG-activated peritoneal macrophages against ActD-untreated L929 tumor cells. Furthermore, we measured the production of hydrogen peroxide (H2O2), nitric oxide (NO) and TNF by macrophages cultured in the presence or absence of L929 cells. As expected, BCG-activated macrophages produced significant amounts of H2O2 (16.0 ± 3.0 µM), TNF (512 U/ml) and NO (71.5 ± 3.2 µM). TNF (256 U/ml) and NO (78.9 ± 9.7 µM) production was unchanged in co-cultures of L929 cells with BCG-activated macrophages but H2O2 production was totally inhibited. The cytotoxic activity was dependent on NO release since L-NAME (2.5, 5.0 and 10 mM), which blocks NO synthase, inhibited the killing of L929 cells. Addition of anti-TNF (20 µg/ml) antibodies to the cultures did not affect the tumoricidal activity of macrophages. Our results indicate that macrophage-mediated killing of L929 cells is largely dependent on NO production but independent of H2O2 or TNF release. (AU)

• Processo FAPESP: 96/12521-8 - Citocinas na ativacao de macrofagos por lectinas, celulas tumorais e superantigenos.
• Beneficiário: Flavia Raquel Fernandes Do Nascimento
• Modalidade de apoio: Bolsas no Brasil - Doutorado