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Suramin effects on macrophage phagolysosome formation and antimicrobial activity
Abstract:
The effects of suramin on phagolysosome formation and antimicrobial activity of mouse peritoneal macrophages cultivated in vitro have been studied. Prolonged in vitro pretreatment of macrophages with high concentrations of suramin caused macrophages to form large fragile phagolysosomes in which the concentrations of the various lysosomal enzymes were inferred to be diminished. In addition, suramin-treated macrophages demonstrated enhanced exocytosis of acid phosphatase during phagocytosis of polyvinyl toluene spherules. However, suramin was found not to inhibit formation of phagolysosomes in macrophages that had ingested Listeria monocytogenes when those cells were examined by the electron microscope. Suramin pretreatment did not alter the ingestion or intracellular killing of Staphylococcus aureus or of a strain of L. monocytogenes that was essentially avirulent for mice, but did protect macrophages from destruction by virulent L. monocytogenes ingested in vitro, an effect that appeared to have been mediated through enhancement of the bacteriostatic potential of the macrophages. However, at a single dosage level, the drug did not alter the mortality of mice challenged with virulent L. monocytogenes.
Insights
Suramin affects macrophage phagolysosomes, potentially reducing enzyme concentrations. It protects macrophages from Listeria monocytogenes but doesn't alter mouse mortality.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophages are crucial immune cells involved in phagocytosis and pathogen killing.
- Phagolysosome formation and lysosomal enzyme activity are key to macrophage antimicrobial function.
Purpose of the Study:
- To investigate the impact of suramin on mouse peritoneal macrophage phagolysosome formation and antimicrobial activity in vitro.
- To assess suramin's effects on lysosomal enzyme concentrations and exocytosis.
- To determine suramin's influence on macrophage interaction with Listeria monocytogenes and Staphylococcus aureus.
Main Methods:
- In vitro culture of mouse peritoneal macrophages.
- Pretreatment with varying concentrations of suramin.
- Assessment of phagolysosome formation and integrity using electron microscopy.
- Measurement of lysosomal enzyme activity and exocytosis.
- Evaluation of macrophage survival and intracellular killing of bacteria (L. monocytogenes, S. aureus).
Main Results:
- High suramin concentrations led to fragile phagolysosomes with diminished lysosomal enzyme concentrations.
- Suramin-treated macrophages showed enhanced acid phosphatase exocytosis during phagocytosis.
- Suramin did not inhibit phagolysosome formation with Listeria monocytogenes.
- Suramin pretreatment did not affect the killing of Staphylococcus aureus or avirulent L. monocytogenes.
- Suramin protected macrophages against virulent L. monocytogenes, enhancing bacteriostatic potential.
- Suramin did not alter mouse mortality when challenged with virulent L. monocytogenes.
Conclusions:
- Suramin significantly alters macrophage phagolysosome characteristics and enzyme activity in vitro.
- Suramin confers protection to macrophages against virulent L. monocytogenes through enhanced bacteriostasis.
- The in vitro effects of suramin on macrophages do not directly translate to altered in vivo survival rates in mice challenged with L. monocytogenes.