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Role of cellular proliferation in the stimulation of MPS phagocytic activity
Abstract:
Administration of agents such as stilboestrol, endotoxin, C. parvum and zymosan, which enhance the phagocytic activity of the mononuclear phagocyte system, also stimulated cellular proliferation in the liver and spleen as assessed by [13H] thymidine incorporation into these organs, and by autoradiography and the number of mitoses in the liver. Sublethal whole body irradiation abolished the proliferative response to stimulation and also reduced or prevented the increase in phagocytic activity. This latter effect depended on the stimulatory agent used, dose of radiation and time of irradiation with respect to stimulation. The results indicate that cell proliferation is important for the increase in phagocytic activity after administration of C. parvum, zymosan and stilboestrol. Endotoxin, however, appears to act primarily by increasing the capacity of existing cells while at the same time causing cell proliferation. The population of cells responding to zymosan by increased phagocytic activity through proliferation was shown to be resident in the liver.
Insights
Stimulating the mononuclear phagocyte system with agents like C. parvum and zymosan enhances phagocytic activity and cell proliferation. Irradiation inhibits this response, suggesting proliferation is key for increased phagocytosis.
Area of Science:
- Immunology
- Cell Biology
- Hepatology
Background:
- The mononuclear phagocyte system (MPS) plays a crucial role in immune responses.
- Agents like C. parvum, zymosan, endotoxin, and stilboestrol are known to enhance MPS phagocytic activity.
- The relationship between MPS stimulation, cellular proliferation, and phagocytic capacity requires further elucidation.
Purpose of the Study:
- To investigate the role of cellular proliferation in the enhanced phagocytic activity of the MPS induced by various agents.
- To determine the impact of sublethal irradiation on MPS stimulation and phagocytic responses.
- To identify the specific cell populations involved in the proliferative response to MPS stimulation.
Main Methods:
- Administration of stimulating agents (stilboestrol, endotoxin, C. parvum, zymosan) to assess effects on phagocytic activity and cellular proliferation.
- [3H] thymidine incorporation, autoradiography, and mitotic counts were used to measure proliferation in liver and spleen.
- Sublethal whole-body irradiation was employed to investigate its effect on proliferation and phagocytosis.
Main Results:
- Stimulatory agents increased both phagocytic activity and cellular proliferation in the liver and spleen.
- Sublethal irradiation abolished the proliferative response and diminished or prevented the increase in phagocytic activity.
- The effect of irradiation on phagocytosis varied depending on the agent, radiation dose, and timing.
- Cell proliferation is crucial for enhanced phagocytosis induced by C. parvum, zymosan, and stilboestrol.
- Endotoxin enhances phagocytosis by increasing existing cell capacity and inducing proliferation.
- Resident liver cells were identified as the proliferating population responding to zymosan.
Conclusions:
- Cellular proliferation is a significant mechanism underlying the enhanced phagocytic activity of the mononuclear phagocyte system following stimulation with certain agents.
- Irradiation-induced suppression of proliferation directly impairs the ability of the MPS to increase phagocytic function.
- Distinct mechanisms exist for different stimulatory agents, with endotoxin acting on both existing cells and inducing proliferation, while others rely more heavily on proliferation.