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Ultrastructure of tumor cell interaction with alveolar macrophages stimulated by vitamin A
Abstract:
F344 rats were given vitamin A for four consecutive days and then their alveolar macrophages (AM phi) were obtained by bronchopulmonary lavage of the lung. Compared with unstimulated AM phi, AM phi from rats given vitamin A had more numerous and longer cytoplasmic projections, and these projections had many knobs on their sides and tip. The AM phi became attached to syngeneic mammary adenocarcinoma cells at many focal points and the tumor cells then lost surface microvilli around the contact zones. Detachment of the knobs from the projections on AM phi was often observed in areas of close association between AM phi and tumor cells. The detached knobs were 250 nm in diameter, gave a positive reaction for acid phosphatase, and frequently became attached to the surface of tumor cells. Then, many of the tumor cells in the vicinity of AM phi exhibited cytolytic changes. It is concluded that the cytotoxicity of stimulated AM phi is due to their attachment to the surface of tumor cells and their release of particles with acid phosphatase activity into the narrow space between the cells, and then to uptake of these particles by susceptible tumor cells.
Insights
Vitamin A enhances alveolar macrophages (AM phi) to attack tumor cells. These activated macrophages release enzyme-containing particles that damage cancer cells, demonstrating a novel mechanism for cancer immunotherapy.
Area of Science:
- Immunology
- Cell Biology
- Oncology
Background:
- Alveolar macrophages (AM phi) play a role in immune surveillance.
- Vitamin A is known to modulate immune cell function.
Purpose of the Study:
- To investigate the effect of vitamin A on alveolar macrophage (AM phi) morphology and cytotoxic activity against tumor cells.
- To elucidate the mechanism by which vitamin A-stimulated AM phi exert cytotoxicity.
Main Methods:
- F344 rats were administered vitamin A for four consecutive days.
- Alveolar macrophages (AM phi) were isolated via bronchopulmonary lavage.
- Interaction between AM phi and syngeneic mammary adenocarcinoma cells was observed using microscopy.
- Cytochemical analysis was performed on detached macrophage components.
Main Results:
- Vitamin A treatment increased the number and length of cytoplasmic projections on AM phi.
- These projections formed attachments with tumor cells, leading to loss of tumor cell microvilli.
- Detached macrophage components (knobs), 250 nm in diameter and positive for acid phosphatase, adhered to tumor cells.
- Tumor cells in proximity to stimulated AM phi showed cytolytic changes.
Conclusions:
- Vitamin A stimulates alveolar macrophages (AM phi), enhancing their cytotoxic potential.
- Cytotoxicity is mediated by the release of acid phosphatase-containing particles from AM phi.
- These particles are internalized by tumor cells, leading to cytolysis.