Induction of Suppressor Macrophages by 12-O-Tetradecanoylphorbol-13-Acetate in Phorbol Ester-Sensitive (SENCAR) and Resistant (B6C3F1) Mice

Abstract

Following topical application of 8 μg 12-O-tetradecanoylphorbol-13-acetate (TPA) twice in one week, the ability of splenic macrophages (Møs) isolated from phorbol ester-sensitive (SENCAR) and resistant (B6C3F1) mice to suppress the phytohemagglutinin (PHA)-induced lymphocyte blastogenesis and NK activity mediated by spleen cells from naive animals was determined. In B6C3F1 mice, suppression of lectin-induced lymphocyte blastogenesis was mediated by MøS from TPA-dosed animals. Alternatively, in TPA-dosed SENCAR mice, induction of MøS suppressive to lectin responses was not apparent. In addition, suppressor MøS did not mediate the decreased splenic natural killer (NK) activity that is characteristically observed in TPA-dosed SENCAR mice. Therefore, it is proposed that the decreased PHA responsiveness and NK activity observed in vivo in TPA-dosed SENCAR mice may be the result of a decreased proportion of lectin-responding T cells and NK cells in the spleen as a result of proliferation of inflammatory cell precursors.