Fc gammaRIII-mediated regulation of hematopoiesis in murine bone marrow cells by interleukin-3 and CD95 (Fas/Apo-1).
The interleukin-3 (IL-3)-dependent murine bone marrow-derived cell line FDC-P2/185-4 (185-4) undergoes apoptosis when IL-3 is withdrawn from culture medium. Previous results from our studies indicated that a high concentration of aggregated mouse IgG prevented apoptosis of 185-4 cells through Fc gammaRIII by an autocrine mechanism, producing IL-3. But after 24 hours, 185-4 cells expressed CD95 (Fas/Apo-1) on their surfaces on stimulation via Fc gammaRIII. In addition, this CD95 was functional and apoptosis was induced by anti-CD95 monoclonal antibody (MoAb). We investigated how these conflicting effects were induced by Fc gammaRIII stimulation within the context of cell survival and death. The results showed that IL-3 was induced by calcium ionophore and that the IL-3 induced by Fc gammaRIII stimulation was blocked by EGTA or FK506, but not by staurosporine (protein kinase C [PKC] inhibitor), indicating the important role of calcium-calcineurin in this system. On the other hand, the CD95 expression induced by Fc gammaRIII stimulation was blocked by staurosporine, but not by EGTA or FK506, and phorbol myristate acetate (PMA) induced CD95 expression in the same manner as Fc gammaRIII, indicating the involvement of PKC in the CD95 expression induced by Fc gammaRIII stimulation. Thus, Fc gammaRIII-mediated stimulation even while promoting immediate survival of the bone marrow cells, also triggers mechanisms that will facilitate their eventual deletion at the end of the response. These results suggest that a balance between cell survival and death is maintained to avoid unlimited cell growth caused by Fc gammaRIII-ligand interaction in hematopoiesis during inflammation.
Yoshikawa
H
H
Department of Parasitology and Immunology, Yamanashi Medical University, Japan.
Sakihama
T
T
Nakajima
Y
Y
Tasaka
K
K
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D011961:Receptors, Fc / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology; D019014:fas Receptor / Q000276:immunology*
D002614:Chelating Agents; D007166:Immunosuppressive Agents; D007377:Interleukin-3; D011961:Receptors, Fc; D019014:fas Receptor; D004533:Egtazic Acid; D016559:Tacrolimus