Acetylspiramycin and the immune system. I. Effects of acetylspiramycin on phagocytosis by mouse macrophages in vitro and in vivo

A study was made of the effect of acetylspiramycin (ASPM) on the phagocytic activity of mouse macrophages in vitro and in vivo, using opsonized, 51Cr-labelled sheep red blood cells (SRBC) as test particles. Resident mouse peritoneal macrophages cultured with ASPM (25-100 micrograms/ml for 18 h) showed a 62-92% reduction in phagocytosis. This was due to decreases in both attachment and ingestion of SRBC and was additional to the detachment of some macrophages from the surface of the culture chamber. Morphologically the macrophages were vacuolated, with some nuclear condensation. When the cells were cultured for a further 48 h after removal of ASPM there was almost complete functional and morphological recovery. When mice were treated with ASPM (50-100 mg/kg orally for 7 days) their peritoneal macrophages showed increases of 57-121% in phagocytic activity in vitro. In mice treated with ASPM (200 mg/kg orally for 7-21 days) the clearance of i.v. injected opsonized SRBC was significantly accelerated. Thus, although ASPM is reversibly toxic to macrophages in vitro, it is not toxic in vivo, but actually stimulates the mononuclear phagocyte system. It is possible that metabolites of ASPM, such as neospiramycin, produced in vivo but not in vitro, are responsible for the stimulation.