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Oxygen radical release by adherent cell populations during the initial stages of a lethal rodent malarial infection
Abstract:
A series of experiments was carried out to assess the levels of reactive oxygen intermediates (ROI) released by macrophages and monocytes during an acute malarial infection, and to consider the importance of oxidant-induced parasite killing in host protection. Adherent cell populations were removed from the peritoneum and spleen of BALB/c and B10/D2/n mice between Days 0-5 of a Plasmodium yoelii nigeriensis infection. These cell populations were quantified, characterized and their ROI-releasing capacity was measured by following ferricytochrome c reduction upon stimulation with phorbol myristate acetate (PMA). Both strains of mice displayed higher numbers of macrophages and macrophage precursors as the infection progressed; this rise was more marked and accompanied by splenomegaly in BALB/c mice. A concurrent decrease in peritoneal cell numbers was observed. Splenic adherent cell populations released much lower levels of ROI than peritoneal macrophages upon triggering. The levels of ROI released from BALB/c splenic adherent cells rose gradually until Day 3, when the parasitaemia was slightly decreased. In contrast, splenic populations from B10 mice had a decreased capacity to release ROI, particularly after Day 3, when the parasitaemia rose sharply. In further studies, electron microscopy was used to detect H2O2 release during the in vitro interaction of peritoneal macrophages and parasitized erythrocytes. Cerium chloride staining techniques demonstrated that H2O production was not dependent on phagocytosis or the presence of immune serum, although levels were increased by the presence of the latter.
Insights
Host immune cells, like macrophages, release reactive oxygen intermediates (ROI) during malaria. This study investigates ROI production by monocytes and macrophages in mice infected with Plasmodium yoelii nigeriensis.
Area of Science:
- Immunology
- Infectious Diseases
- Cell Biology
Background:
- Acute malarial infections trigger immune responses involving macrophages and monocytes.
- Reactive oxygen intermediates (ROI) are implicated in host defense mechanisms against pathogens.
- Understanding the role of ROI in malaria pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To quantify ROI release from macrophages and monocytes during Plasmodium yoelii nigeriensis infection in mice.
- To assess the contribution of oxidant-induced parasite killing to host protection.
- To compare ROI production between different mouse strains (BALB/c and B10/D2/n) during infection.
Main Methods:
- Isolation and characterization of peritoneal and splenic adherent cells from infected mice.
- Measurement of ROI-releasing capacity using ferricytochrome c reduction assay upon phorbol myristate acetate (PMA) stimulation.
- Electron microscopy with cerium chloride staining to detect hydrogen peroxide (H2O2) release during macrophage-parasitized erythrocyte interaction.
Main Results:
- Increased numbers of macrophages and precursors observed in both mouse strains as infection progressed, with marked splenomegaly in BALB/c mice.
- Splenic adherent cells released significantly lower ROI levels compared to peritoneal macrophages.
- BALB/c splenic cells showed increased ROI release until Day 3, while B10 mice exhibited decreased ROI release capacity after Day 3.
- Hydrogen peroxide (H2O2) production by peritoneal macrophages was not dependent on phagocytosis or immune serum, but was enhanced by immune serum.
Conclusions:
- Macrophages and monocytes play a role in generating ROI during acute malaria.
- Differences in ROI production capacity exist between mouse strains and between peritoneal and splenic macrophages.
- Oxidative stress generated by immune cells may contribute to parasite control during malaria.