Nitric oxide synthesis contributes to IL-2-induced antitumor responses against intraperitoneal Meth A tumor

C. Y. Yim, J. R. McGregor, O. D. Kwon, N. R. Bastian, M. Rees, Motomi (Tomi) Mori, J. B. Hibbs, W. E. Samlowski

Research output: Contribution to journalArticle

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Abstract

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 μM vs 3.2 ± 1.5 μM in untreated controls). N(ω)- 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.

Original languageEnglish (US)
Pages (from-to)4382-4390
Number of pages9
JournalJournal of Immunology
Volume155
Issue number9
StatePublished - 1995
Externally publishedYes

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Interleukin-2
Nitric Oxide
Neoplasms
Arginine
Lymphokine-Activated Killer Cells
Ascites
Macrophages
Electron Spin Resonance Spectroscopy
Skin Neoplasms
Nitrites
Heme
Nitric Oxide Synthase
Nitrates
Spectrum Analysis
Therapeutics
Cell Proliferation
Lymphocytes
Survival

ASJC Scopus subject areas

  • Immunology

Cite this

Yim, C. Y., McGregor, J. R., Kwon, O. D., Bastian, N. R., Rees, M., Mori, M. T., ... Samlowski, W. E. (1995). Nitric oxide synthesis contributes to IL-2-induced antitumor responses against intraperitoneal Meth A tumor. Journal of Immunology, 155(9), 4382-4390.

Nitric oxide synthesis contributes to IL-2-induced antitumor responses against intraperitoneal Meth A tumor. / Yim, C. Y.; McGregor, J. R.; Kwon, O. D.; Bastian, N. R.; Rees, M.; Mori, Motomi (Tomi); Hibbs, J. B.; Samlowski, W. E.

In: Journal of Immunology, Vol. 155, No. 9, 1995, p. 4382-4390.

Research output: Contribution to journalArticle

Yim, CY, McGregor, JR, Kwon, OD, Bastian, NR, Rees, M, Mori, MT, Hibbs, JB & Samlowski, WE 1995, 'Nitric oxide synthesis contributes to IL-2-induced antitumor responses against intraperitoneal Meth A tumor', Journal of Immunology, vol. 155, no. 9, pp. 4382-4390.
Yim, C. Y. ; McGregor, J. R. ; Kwon, O. D. ; Bastian, N. R. ; Rees, M. ; Mori, Motomi (Tomi) ; Hibbs, J. B. ; Samlowski, W. E. / Nitric oxide synthesis contributes to IL-2-induced antitumor responses against intraperitoneal Meth A tumor. In: Journal of Immunology. 1995 ; Vol. 155, No. 9. pp. 4382-4390.
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abstract = "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 μM vs 3.2 ± 1.5 μM in untreated controls). N(ω)- 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.",
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