Related Experiment Videos
Fc receptors expression and function in mononuclear phagocytes from AIDS patients: modulation by IFN-gamma
F Capsoni1, F Minonzio, A M Ongari
1Institute of Internal Medicine, Infectious Diseases and Immunopathology, University of Milan, Italy.
Abstract:
Fc-receptor (FcR)-mediated phagocytosis and FcR (FcRI, FcRII and FcRIII) membrane expression was studied on freshly separated and cultured monocytes (Mo) from 20 AIDS patients and 20 healthy controls. Both Mo and Mo-derived macrophages from AIDS patients presented a significant defect in their capacity to ingest IgG-coated erythrocytes (EA) compared to control cells. This functional defect did not depend on a decline in the number of FcR+ cells or on a decrease in the expression of FcR on their surface. In fact, the percentages of phagocytes reacting with anti-FcRI MoAb (32.2) or anti-FcRII MoAb (IV.3) were similar for controls and AIDS patients, while the percentage of FcRIII-positive Mo (MoAb 3G8) was higher in the AIDS population than in controls, though this difference was not seen on cultured Mo. The level of FcRI expression, evaluated as mean fluorescence intensity (MFI), was higher on freshly separated Mo from AIDS patients than from controls but this difference disappeared also with differentiation of Mo to Mo-derived macrophages in vitro. Parallel analysis of FcRII and FcRIII on phagocytes revealed no differences in the MFI between the AIDS and control groups. Some observations suggested that this functional defect might be secondary to phagocyte priming by circulating IFN-gamma: (1) in vitro stimulation of Mo with hrIFN-gamma, which increased FcRI expression, actually reduced phagocytosis of IgG-coated particles; and (2) IFN-gamma concentrations were increased in AIDS patients' plasma. In spite of these findings, no significant correlation was found between plasma IFN-gamma concentrations and FcR-mediated ingestion in AIDS patients, making the hypothesis uncertain. Even if the basis for the impaired FcR-mediated phagocytosis in AIDS patients remains unclear, this functional defect may have a role in the immunopathogenesis of AIDS, constituting a component cause of the immunodeficiency.
Insights
Monocytes from AIDS patients show impaired IgG-coated particle ingestion, despite normal Fc receptor (FcR) expression. This defect may contribute to immunodeficiency, though its exact cause, possibly related to IFN-gamma, remains uncertain.
Area of Science:
- Immunology
- Cell Biology
Background:
- Acquired immunodeficiency syndrome (AIDS) is characterized by profound immune dysfunction.
- Fc receptors (FcRs) on monocytes play a crucial role in phagocytosis and immune responses.
Purpose of the Study:
- To investigate Fc receptor (FcR)-mediated phagocytosis and FcR expression on monocytes from AIDS patients.
- To determine if impaired phagocytosis in AIDS is linked to FcR expression levels or other factors.
Main Methods:
- Studied FcR-mediated phagocytosis and FcR (FcRI, FcRII, FcRIII) membrane expression on monocytes (Mo) from AIDS patients and healthy controls.
- Utilized IgG-coated erythrocytes (EA) for phagocytosis assays and monoclonal antibodies (MoAb) for FcR expression analysis.
- Assessed FcR expression using mean fluorescence intensity (MFI) and flow cytometry.
Main Results:
- Monocytes and macrophages from AIDS patients exhibited a significant defect in ingesting IgG-coated erythrocytes compared to controls.
- This phagocytic defect was not attributable to reduced FcR-positive cell numbers or decreased FcR surface expression.
- While FcRI expression was higher on freshly isolated AIDS monocytes, this difference diminished upon differentiation; FcRII and FcRIII expression showed no significant differences in MFI.
- In vitro studies suggested a potential role for interferon-gamma (IFN-γ) in impairing phagocytosis, but direct correlation with plasma IFN-γ levels was not found.
Conclusions:
- AIDS patients display impaired FcR-mediated phagocytosis in monocytes, independent of FcR expression levels.
- The precise mechanism underlying this functional defect remains unclear, with IFN-γ involvement being a plausible but unconfirmed hypothesis.
- This impaired phagocytic capacity may contribute to the immunopathogenesis of AIDS and the overall immunodeficiency observed in patients.