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Treatment with progesterone analogues decreases macrophage Fcgamma receptors expression
1Department of Medicine, Hospital Universitario de Puerto Real/S.A.S., Spain.
Abstract:
Macrophage Fcgamma receptors (FcgammaRs) are critical for host defense against infection and have an important role in immune cytopenias. Modulation of macrophage FcgammaRs expression is a potential therapeutic approach to immune disorders. Glucocorticoids and synthetic progesterone analogues decrease macrophage FcgammaRs expression. We assessed the effect of treatment with commonly employed progestins on the expression of macrophage FcgammaRs using an experimental model in the guinea pig. Eight clinically available progesterones, medroxyprogesterone acetate (P3), megestrol acetate (P4), medrogestone (P5), alylestrenol (P6), linestrenol (P7), didrogesterone (P8), norethisterone (P9), and gestonorone caproate (P10) and two endogenous progesterones, progesterone (P1) and 17 alpha-hydroxyprogesterone (P2), were studied. Following in vivo treatment of guinea pigs, we determined the clearance of IgG-sensitized erythrocytes in vivo, the binding of IgG-sensitized erythrocytes by isolated splenic macrophages, and splenic macrophage Fcgamma receptor cell surface expression. All progesterones impaired the clearance of IgG-sensitized erythrocytes by decreasing splenic macrophage Fcgamma receptor expression. P5, P6, P7, and P8 were less effective. Flow cytometry and fluorescence microscopy with monoclonal antibodies demonstrated that progesterones decreased the cell surface expression of FcgammaR2 more than that of FcgammaR1,2. Clinically employed progestins impair the clearance of IgG-coated cells by decreasing splenic macrophage FcgammaRs expression. Thus, progesterones are candidate drugs for the treatment of immune disorders.
Insights
Progestins, a class of drugs, reduce macrophage Fc gamma receptors (FcgammaRs) expression, impairing the clearance of antibody-coated cells. This suggests progestins could treat immune disorders by modulating FcgammaRs.
Area of Science:
- Immunology
- Pharmacology
Background:
- Macrophage Fc gamma receptors (FcgammaRs) are crucial for immune responses and implicated in immune cytopenias.
- Modulating FcgammaRs expression presents a therapeutic strategy for immune disorders.
- Glucocorticoids and synthetic progestins are known to decrease FcgammaRs expression.
Purpose of the Study:
- To investigate the impact of various progestins on macrophage FcgammaRs expression and function in an experimental model.
- To determine if clinically used progestins can be candidates for treating immune disorders.
Main Methods:
- In vivo administration of eight clinically available and two endogenous progestins to guinea pigs.
- Assessment of IgG-sensitized erythrocyte clearance and binding by splenic macrophages.
- Quantification of splenic macrophage Fcgamma receptor cell surface expression using flow cytometry and fluorescence microscopy.
Main Results:
- All studied progestins impaired the clearance of IgG-sensitized erythrocytes.
- This impairment was associated with decreased splenic macrophage Fcgamma receptor expression.
- Progestins predominantly reduced FcgammaR2 expression compared to FcgammaR1,2.
Conclusions:
- Clinically employed progestins reduce the clearance of IgG-coated cells by downregulating macrophage FcgammaRs.
- Progestins demonstrate potential as therapeutic agents for immune disorders by modulating FcgammaRs.
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