| Autor: |
C Y, Yim, J R, McGregor, O D, Kwon, N R, Bastian, M, Rees, M, Mori, J B, Hibbs, W E, Samlowski |
| Rok vydání: |
1995 |
| Předmět: |
|
| Zdroj: |
Journal of immunology (Baltimore, Md. : 1950). 155(9) |
| ISSN: |
0022-1767 |
| Popis: |
IL-2 therapy is a potent inductive stimulus for nitric oxide (NO.) synthesis in mice and humans. It is not yet clear whether NO. can contribute to IL-2-induced therapeutic responses. The murine skin cancer Meth A is relatively resistant to lymphokine-activated killer (LAK) cell killing, allowing evaluation of the role of IL-2-induced NO. synthesis in vivo, without contribution by LAK cells. Subcutaneous IL-2 treatment of mice bearing i.p. Meth A tumor increased nitrite production by cells derived from ascites (63 +/- 14 microM vs 3.2 +/- 1.5 microM in untreated controls). N omega-monomethyl-L-arginine (MLA), NO. synthase inhibitor, prevented this increase. NO. production correlated in an inverse fashion with tumor cell proliferation in vitro. Evidence for IL-2-induced heme nitrosylation was demonstrated in tumor cells by electron paramagnetic resonance spectroscopy. By immunomagnetic depletion experiments, macrophages were implicated as a major source of NO. synthesis. Cytologic and flow-cytometric evaluation revealed that IL-2 treatment resulted in enhanced lymphocyte and macrophage recruitment into malignant ascites, and decreases in tumor cell recovery. MLA administration further increased host cell recovery. Subcutaneous IL-2 therapy increased urinary nitrate excretion up to eightfold in mice, and appeared to produce a significant survival advantage that was prevented by MLA administration. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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