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Activation of antitumor properties in alveolar macrophages from protein-calorie malnourished rats
Abstract:
Protein-calorie malnutrition (PCM) was induced by feeding male F344 rats on a 5% casein diet for 7 weeks. At appropriate times, rats from control (20% casein diet) and PCM groups were killed and alveolar macrophages (AM) were obtained by bronchoalveolar lavage. The functional integrity of the AM was determined by measuring their ability to become tumoricidal on treatment with macrophage activators, such as muramyl dipeptide (MDP) or multilamellar liposomes containing MDP or its lipophilic analog, MTP-PE. After 5 and 7 weeks, the numbers of lavaged AM per gram body weight of rats were much higher in the PCM group than in the control group. In week 3, AM from the PCM group showed spontaneous tumoricidal activity against syngeneic tumor cells, but in weeks 5 and 7 they did not. However, AM from PCM rats behaved the same way as controls in their response to activation stimuli in vitro with multilamellar liposomes containing synthetic MDP or MTP-PE. These data show that PCM affects the number of AM, but that AM from rats in a state of PCM become tumoricidal in response to activation stimuli in vitro.
Insights
Protein-calorie malnutrition (PCM) increases alveolar macrophage numbers in rats. While initially tumoricidal, these macrophages regain function when stimulated in vitro, suggesting potential therapeutic avenues.
Area of Science:
- Immunology
- Nutrition Science
- Cell Biology
Background:
- Protein-calorie malnutrition (PCM) significantly impacts immune function.
- Alveolar macrophages (AM) play a crucial role in lung immunity and host defense.
- Understanding AM behavior during malnutrition is vital for assessing immune status.
Purpose of the Study:
- To investigate the effects of PCM on the number and function of rat alveolar macrophages.
- To assess the tumoricidal capacity of AM from malnourished rats.
- To determine the responsiveness of AM from PCM rats to in vitro activation stimuli.
Main Methods:
- Induction of PCM in male F344 rats using a 5% casein diet for 7 weeks.
- Collection of alveolar macrophages (AM) via bronchoalveolar lavage from control and PCM groups.
- Assessment of AM tumoricidal activity and response to macrophage activators (muramyl dipeptide, liposomes with MDP or MTP-PE).
Main Results:
- PCM significantly increased the number of lavaged AM per gram body weight compared to controls.
- AM from PCM rats exhibited spontaneous tumoricidal activity at week 3, which diminished by weeks 5 and 7.
- AM from PCM rats responded comparably to control AM when activated in vitro with liposomal MDP or MTP-PE.
Conclusions:
- PCM alters the quantity of alveolar macrophages in rats.
- While spontaneous tumoricidal activity may be transiently affected, AM from PCM rats retain the capacity for activation and tumoricidal function in response to specific stimuli.
- These findings highlight the complex interplay between malnutrition and macrophage immune competence.