Changes in the expression of macrophage antigens associated with activation for tumor cell killing

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Abstract
Cultured murine bone marrow macrophages (BMMΦ) can be induced to kill tumor cells in vitro by combined treatment with a priming (IFN-γ) and a triggering (LPS) agent. We have examined the expression of cellular antigens accompanying this activation by Western biot analysis with rabbit antisera raised against unstimulated and fully activated BMMΦ and assayed the effect of these antisera on macrophage-mediated tumor cytotoxicity. Killing of Yac-1 target cells was slightly enhanced by antiserum against unstimulated BMMΦ but inhibited 54% by antiserum against activated BMMΦ. The following changes in antigen expression are shown to be associated with discrete stages of activation and localized to the cytosolic or membrane fractions. Antigens with apparent molecular weights of 109, 67, and 48 kd are expressed after priming with IFN-γ whereas LPS induces the enhanced expression of antigens with molecular weights of 46, 30, and 14.4 kd. One antigen with a molecular weight of 54 kd apparently is only expressed by fully activated BMMΦ treated with a combination of IFN-γ and LPS. Antigens with molecular weights of 170 and 21 kd are repressed by LPS and IFN-γ respectively. IFN-γ partially counteracts changes induced by treatment with LPS alone when used in combination with LPS. All antigens are localized in the cytosolic fraction except the 54 kd and to some extent the 30 kd, which were detected in the membrane traction. The 21 kd was only detectable in crude lysates and thus presumably is of nuclear origin. The 48 kd antigen can also be detected in conditioned culture supernatants of fully activated BMMΦ, which express tumorilytic activity of their own, and thus may be directly involved in cytolytic macrophage effector functions.

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