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Functional and phenotypic changes associated with the in vitro development of human monocytes into activated
1University Department of Pathology, Southampton General Hospital, U.K.
Abstract:
Freshly isolated human peripheral blood monocytes had minimal cytotoxic effect in vitro on the schistosomula of Schistosoma mansoni. However, stimulation of the cells with either interferon gamma (IFN) or specific anti-parasite antiserum caused an increase in cytotoxicity. Additionally, the normal development of monocytes into macrophages over 7 days was associated with a sharp increase in cytotoxicity. The non-cytotoxic monocytes were compared with activated macrophages to assess whether cytotoxicity was associated with changes in immunophenotype. As monocytes developed into macrophages there were marked increases in transferrin receptors (HB21), macrophage cellular integrin (3.9), and Fc receptors (KB61). A further three markers showed increased expression in 7-day-old macrophages stimulated by IFN, namely a high affinity Fc gamma receptor (10.1), MHC Class II (1B5) and tumour necrosis factor (TNF).
Insights
Human monocytes showed limited cytotoxicity against Schistosoma mansoni parasites. Activation with interferon gamma (IFN) or antiserum, and maturation into macrophages, significantly enhanced this parasite-killing ability.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Monocytes are key immune cells with varying cytotoxic potential.
- Schistosoma mansoni is a parasitic worm causing significant human disease.
- Understanding monocyte-macrophage differentiation and activation is crucial for immune response.
Purpose of the Study:
- To investigate the in vitro cytotoxic effects of human monocytes on Schistosoma mansoni.
- To determine how monocyte activation and differentiation into macrophages influence cytotoxicity.
- To correlate changes in immunophenotype with enhanced cytotoxic activity.
Main Methods:
- Isolated human peripheral blood monocytes were cultured for 7 days to allow differentiation into macrophages.
- Monocytes and macrophages were stimulated with interferon gamma (IFN) or anti-parasite antiserum.
- Cytotoxicity assays were performed against schistosomula of Schistosoma mansoni.
- Immunophenotyping was conducted using specific markers to assess cell surface receptor expression.
Main Results:
- Freshly isolated monocytes exhibited minimal cytotoxicity against schistosomula.
- Cytotoxicity significantly increased upon stimulation with IFN or antiserum, and with monocyte-macrophage differentiation.
- Macrophage differentiation led to increased expression of transferrin receptors, cellular integrin, and Fc receptors.
- IFN-stimulated macrophages showed further upregulation of Fc gamma receptor, MHC Class II, and tumor necrosis factor (TNF).
Conclusions:
- Monocyte differentiation into macrophages and activation by IFN or antiserum are critical for developing potent anti-schistosomula cytotoxicity.
- Enhanced cytotoxicity is associated with significant changes in macrophage immunophenotype, including increased expression of specific receptors and molecules.
- These findings highlight the plasticity of monocytes and their potential to become effective effector cells against parasitic infections.