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Pharmacological modulation of the IFNgamma-induced accessory function of alveolar macrophages and peripheral blood
1Research Center Borstel, Medical Hospital, Germany. gzissel@fz-borstel.de
Objective And Design:
Although alveolar macrophages (AM) are poor accessory cells, alveolar macrophages of patients with sarcoidosis or tuberculosis show an elevated accessory function indicating that the accessory function (AF) of AM can be upregulated.
Materials And Methods:
We examined whether the AF of AM and peripheral blood monocytes (PBM) can be increased by interferon-gamma (IFNgamma) and whether immunomodulating drugs like cyclosporine A, cyclophosphamide, dexamethasone, and ambroxol are able to modulate the accessory function and the expression of accessory molecules.
Results:
IFNgamma increased the AF of AM and PBM up to 309 +/- 122% and 152 +/- 25%, respectively (p < 0.02, unstimulated control = 100%, in all cases). In alveolar macrophages this increase is most efficiently prevented by cyclosporine A (31 +/- 13%), followed by cyclophosphamide (64 +/- 20%) and dexamethasone (66 +/- 20%). In monocytes the IFNgamma-induced increase in accessory function is prevented only by cyclosporine A (17 +/- 7%) and dexamethasone (59 +/- 9%). Cyclosporine A was also the most effective drug downregulating the expression of accessory molecules (CD54, CD58, CD80 and CD86).
Conclusions:
In summary, the accessory function of alveolar macrophages and monocytes is upregulated by IFNgamma and can be controled by immunomodulating drugs.
Insights
Interferon-gamma upregulates the accessory function of alveolar macrophages and monocytes. Immunomodulating drugs, particularly cyclosporine A, can control this enhanced function and molecule expression.
Area of Science:
- Immunology
- Cell Biology
Background:
- Alveolar macrophages (AM) typically exhibit limited accessory cell function.
- Elevated accessory function in AM from sarcoidosis or tuberculosis patients suggests potential for upregulation.
Purpose of the Study:
- To investigate if interferon-gamma (IFNγ) can enhance the accessory function (AF) of AM and peripheral blood monocytes (PBM).
- To determine if immunomodulating drugs modulate this IFNγ-induced AF and accessory molecule expression.
Main Methods:
- Treatment of AM and PBM with IFNγ.
- Assessment of AF changes post-IFNγ stimulation.
- Evaluation of immunomodulating drugs (cyclosporine A, cyclophosphamide, dexamethasone, ambroxol) on AF and accessory molecule expression (CD54, CD58, CD80, CD86).
Main Results:
- IFNγ significantly increased AF in both AM (309%) and PBM (152%).
- Cyclosporine A, cyclophosphamide, and dexamethasone inhibited IFNγ-induced AF in AM, with cyclosporine A being most effective.
- Cyclosporine A and dexamethasone inhibited IFNγ-induced AF in PBM. Cyclosporine A most effectively downregulated accessory molecule expression.
Conclusions:
- The accessory function of AM and PBM can be upregulated by IFNγ.
- Immunomodulating drugs, especially cyclosporine A, can effectively control IFNγ-induced accessory function and molecule expression in these cells.