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Phenotypic characterization of gamma interferon-induced human monocyte polykaryons
Blood
|December 1, 1985
Summary
Gamma interferon (IFN-gamma) induces fusion of monocytes into multinucleated giant cells (macrophage polykaryons [MPs]). These IFN-gamma-induced MPs exhibit distinct characteristics compared to uninuclear monocytes (UMs), impacting phagocytosis and cell surface antigen expression.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Multinucleated giant cells, termed macrophage polykaryons (MPs), originate from mononuclear phagocytes like monocytes or macrophages.
- These MPs are observed in various physiological and pathological conditions.
- Previous research demonstrated that gamma interferon (IFN-gamma) promotes the fusion of uninuclear monocytes (UMs) to form MPs.
Purpose of the Study:
- To thoroughly characterize the features of macrophage polykaryons (MPs) induced by IFN-gamma.
- To compare the functional and phenotypic properties of IFN-gamma-induced MPs with uninuclear monocytes (UMs).
Main Methods:
- Enzyme activity assays (peroxidase, non-specific esterase, acid phosphatase) were performed on UMs and MPs.
- Phagocytosis assays using polystyrene spheres and erythrocytes (coated and uncoated) were conducted.
- Hydrogen peroxide (H2O2) production and nitroblue tetrazolium (NBT) reduction were measured.
- Flow cytometry was used to analyze the expression of surface membrane antigens and HLA-DR.
- Lectins were employed to assess cell surface binding characteristics.
Main Results:
- IFN-gamma-induced MPs showed depressed phagocytosis of spheres and fixed erythrocytes, and markedly depressed phagocytosis of IgG-coated erythrocytes compared to UMs.
- MPs exhibited reduced H2O2 production and NBT reduction compared to UMs.
- Key surface antigens (Leu M3, OKM1, etc.) were absent or poorly expressed on MPs, while HLA-DR expression was increased.
- Enzyme profiles indicated intense non-specific esterase and acid phosphatase activity, unaffected by tartrate but abolished by fluoride for esterase.
Conclusions:
- Macrophage polykaryons formed by IFN-gamma-induced monocyte fusion in vitro possess distinct biochemical and functional characteristics compared to uninuclear monocytes.
- These differences include altered phagocytic capacity, reduced oxidative burst potential, and differential expression of surface markers.
- The findings highlight the significant cellular changes occurring during monocyte-macrophage differentiation and fusion induced by IFN-gamma.