Brucella abortus causes an accelerated repopulation of the spleen and liver of mice by macrophages after their liposome-mediated depletion.

Abstract

Different macrophage subsets are present in the spleen, i.e., marginal zone macrophages (MZM), marginal metallophilic macrophages (MMM) and red pulp macrophages (RPM) and all are depleted by a single treatment with liposome-encapsulated clodronate. These macrophages can be distinguished by differences in localisation patterns, membrane antigens and repopulation kinetics after depletion. In experiments on the involvement of splenic macrophages in the humoral immune response, there was an acceleration of the repopulation kinetics of all macrophage subsets in the spleen after intravenous injection of an autoclaved suspension of Brucella abortus 544 (BA 544 antigen). The time required to obtain 100% repopulation in macrophage-depleted control mice was 2 weeks for RPM, 6 weeks for MMM and > 2 months for MZM. However, after BA 544 injection, 100% repopulation was obtained within 4 days in the case of RPM and within 2 weeks in the case of MMM. Acid phosphatase activity, indicating the presence of MZM, had returned to normal levels within 2 months. Acceleration of repopulation was observed only after intravenous administration of antigen preparations from Brucella strains (except strain BA 19). Although BA 544 antigen stimulated the proliferation of precursors of all of the macrophage subsets in the spleen and liver, it also affected mature members of the mononuclear phagocyte system such as MZM and dendritic cells in the spleen.