NKG2D dependent killing of Adenovirus serotype 5 E1A expressing tumor cells by bone marrow derived murine macrophages

Abstract

Prior studies indicate that the expression of the adenovirus (Ad) E1A oncoprotein in human fibrosarcoma (H4) or mouse methylchoranthrene‐induced (MCA‐205) tumor cells up‐regulates NKG2D ligands thereby sensitizing these tumor cells to lysis by NK cells. This study examined whether the ability of macrophages to lyse tumor cells that express E1A is also dependent on the expression of the activating NKG2D receptor on the surface of activated macrophages. By FACS and western analysis, we demonstrate that activation of macrophages with LPS and IFN? upregulates the expression of NKG2D. The monoclonal antibody, CX5, which blocks the interaction of NKG2D with NKG2D ligands, abrogated the ability of macrophages to kill H4 or MCA‐205 cells that express E1A. Furthermore, transfection of MCA‐205 cells with the NKG2D ligand, Rae‐1, renders these tumor cells to lysis by macrophages. These data demonstrate that macrophages express NKG2D and that the lysis of tumor cells that express E1A is NKG2D‐NKG2D ligand dependent.