Functional expression of Fas on mouse bone marrow stromal cells: upregulation by tumor necrosis factor-alpha and interferon-gamma.
In this study we describe the expression and function of Fas in mouse bone marrow (BM) stromal cells (SCs) and cell lines derived from long-term BM cultures. Flow cytometry analysis showed that Fas was expressed on adherent cells from freshly isolated BM and on all cloned SC lines tested. The SC line ME-25 was Fas+ but negative for FasL as detected by reverse transcriptase-polymerase chain reaction. Furthermore, ME-25 was CD44+, VCAM-1+, Mac-3-, Gr-1-, and type IV collagen-. ME-25 treatment with interferon-gamma or tumor necrosis factor-alpha significantly induced upregulation of Fas expression as detected by both flow cytometry and Western blot immunoassay. The same treatment with interleukin (IL)-1, IL-2, or IL-13 had no effect. Functional studies demonstrated that Fas induced a strong increase in apoptosis when engaged with an anti-Fas monoclonal antibody (MoAb). Activated BM T cells induced Fas-dependent cytotoxicity of ME-25 insofar as blocking anti-FasL MoAb inhibited the killing of ME-25 induced by activated BM T cells. These data suggest a possible involvement of Fas-expressing SCs in negative regulatory functions in the BM and provide a starting point for further studies on the role of Fas+ SCs.
Lepri
E
E
Department of Clinical and Experimental Medicine, University of Perugia, Italy.
Delfino
D V
DV
Migliorati
G
G
Moraca
R
R
Ayroldi
E
E
Riccardi
C
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019014:fas Receptor / Q000235:genetics* / Q000276:immunology
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D007371:Interferon-gamma