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In vitro effect of lung surfactant on alveolar macrophage defence mechanisms against Cryptococcus neoformans
N T Gross1, P Camner, M Chinchilla
1Department of Immunology, Microbiology, Pathology and Infectious Diseases, Huddinge University Hospital, Sweden.
Abstract:
The effects of a modified natural porcine surfactant (Curosurf) on phagocytosis and killing of Cryptococcus neoformans by alveolar macrophages and on the production of superoxide anions were investigated in vitro. Attachment and ingestion were evaluated separately by a fluorescent quenching technique. The nitroblue tetrazolium reduction test was used as an indirect measurement of superoxide anion production. Killing was assessed by a colony-forming assay. Surfactant induced increased ingestion of C. neoformans, unopsonized as well as opsonized with fresh serum or anticryptococcal polyclonal IgG. Surfactant had, however, no effect on the attachment or killing of unopsonized or opsonized C. neoformans by the alveolar macrophages. In addition, the enhancement of the oxidative metabolism of the macrophages after stimulation with opsonized yeast was impaired, although the killing was not affected. This study indicates that in vitro Curosurf can influence the alveolar macrophage defence against C. neoformans by enhancing its ingestion and by interacting with the superoxide anions release from alveolar macrophages stimulated with fresh serum or anticryptococcal polyclonal IgG opsonized yeast cells.
Insights
Modified porcine surfactant (Curosurf) enhances alveolar macrophage ingestion of Cryptococcus neoformans in vitro. However, it does not affect fungal attachment or killing, and impairs superoxide anion production.
Area of Science:
- Immunology
- Pulmonary Medicine
- Microbiology
Background:
- Alveolar macrophages are crucial for lung defense against fungal pathogens like Cryptococcus neoformans.
- Pulmonary surfactants, like Curosurf, play a role in lung physiology and may interact with immune cells.
Purpose of the Study:
- To investigate the in vitro effects of a modified porcine surfactant (Curosurf) on alveolar macrophage functions.
- To assess Curosurf's impact on the phagocytosis, killing, and oxidative metabolism of Cryptococcus neoformans.
Main Methods:
- In vitro study using alveolar macrophages and Cryptococcus neoformans.
- Fluorescent quenching technique for attachment and ingestion assays.
- Nitroblue tetrazolium test for superoxide anion production.
- Colony-forming assays for fungal killing.
Main Results:
- Curosurf significantly increased the ingestion of both unopsonized and opsonized C. neoformans by macrophages.
- No significant effect of Curosurf on the attachment or killing of C. neoformans was observed.
- Curosurf impaired the enhancement of macrophage oxidative metabolism when stimulated with opsonized yeast.
Conclusions:
- Curosurf enhances the phagocytic capacity of alveolar macrophages towards C. neoformans in vitro.
- Curosurf interacts with macrophage oxidative metabolism but does not compromise the overall killing of C. neoformans.
- These findings suggest Curosurf can modulate macrophage defense mechanisms against Cryptococcus neoformans.