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Effect of Nocardia rubra cell wall skeleton on augmentation of cytotoxicity function in human pleural macrophages
M Sakatani1, T Ogura, T Masuno
1Department of Internal Medicine, National Kinki-Chuo Hospital for Chest diseases, Osaka, Japan.
Abstract:
The ability of Nocardia rubra cell wall skeleton (N-CWS) to augment macrophage cytotoxicity function was examined using human pleural macrophages prepared from 32 malignant pleural effusions and 53 pleural washings. The cytostatic activity of pleural macrophages for human lung cancer cells (PC-9) was augmented following incubation of pleural mononuclear cells with 10 micrograms/ml N-CWS for 24 h. Macrophage activity was increased by direct interaction of macrophages with N-CWS or by incubation of macrophages with supernatant culture fluids from pleural lymphocytes with N-CWS. The cytotoxic potential of the pleural macrophages obtained from patients treated with 500 micrograms of N-CWS intrapleurally was also increased. The heat and acid stability studies revealed that the culture fluids from pleural lymphocytes treated with N-CWS contained macrophage activation factor in addition to interferon-gamma. These results suggest that direct and indirect macrophage activation is part of the mechanism in which N-CWS has a clinical effect on malignant pleural effusions.
Insights
Nocardia rubra cell wall skeleton (N-CWS) enhances macrophage anti-cancer activity against lung cancer cells. This immune activation, observed in malignant pleural effusions, suggests a potential therapeutic role for N-CWS.
Area of Science:
- Immunology
- Oncology
- Microbiology
Background:
- Malignant pleural effusions are often associated with poor prognosis.
- Macrophages play a crucial role in anti-tumor immunity.
- Nocardia rubra cell wall skeleton (N-CWS) is a known immunomodulator.
Purpose of the Study:
- To investigate the effect of N-CWS on the cytotoxic function of human pleural macrophages.
- To explore the mechanisms by which N-CWS activates macrophages in the context of malignant pleural effusions.
Main Methods:
- Human pleural macrophages were isolated from malignant pleural effusions and washings.
- Cells were incubated with N-CWS (10 µg/ml) or supernatant from N-CWS-treated lymphocytes.
- Macrophage cytotoxicity against human lung cancer cells (PC-9) was assessed.
- Heat and acid stability studies were performed on culture fluids.
Main Results:
- N-CWS augmented the cytostatic activity of pleural macrophages against lung cancer cells.
- Macrophage activation occurred through direct interaction with N-CWS or via soluble factors in culture supernatants.
- Intrapleural administration of N-CWS in patients increased pleural macrophage cytotoxicity.
- Culture fluids contained macrophage activation factor and interferon-gamma.
Conclusions:
- N-CWS directly and indirectly activates macrophages, enhancing their anti-cancer potential.
- These findings suggest a mechanism for the clinical efficacy of N-CWS in managing malignant pleural effusions.