Pharmacological modulation of the IFNgamma-induced accessory function of alveolar macrophages and peripheral blood monocytes.
OBJECTIVE
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.


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.
Zissel
G
G
Research Center Borstel, Medical Hospital, Germany. gzissel@fz-borstel.de
Ernst
M
M
Schlaak
M
M
Müller-Quernheim
J
J
D000368:Aged; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016572:Cyclosporine / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects*; D011994:Recombinant Proteins; D017565:Sarcoidosis, Pulmonary / Q000473:pathology
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016572:Cyclosporine