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 micrograms 12-O-tetradecanoylphorbol-13-acetate (TPA) twice in one week, the ability of splenic macrophages (M phi s) 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 M phi s from TPA-dosed animals. Alternatively, in TPA-dosed SENCAR mice, induction of M phi s suppressive to lectin responses was not apparent. In addition, suppressor M phi s 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.