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Macrophage progenitor cell and colony-stimulating factor production during granulomatous schistosomiasis mansoni in mice

Schistosoma mansoni worm eggs stimulate a T-cell-mediated granulomatous response in which macrophages play important inflammatory and regulatory roles. Although much has been learned about the functions of the schistosome granuloma macrophages, their origin and replicative ability are unknown. In the present sequential study, macrophage progenitor cells in the bone marrow (GM-CFC) and liver granulomas (M-CFC) were enumerated, and macrophage colony-stimulating factor (CSF-1) in the circulation and culture fluid of explanted granulomas of infected mice was assayed. During the acute phase of the infection, when the granulomatous response was vigorous (weeks 8 to 12) GM-CFC numbers were high in the bone marrow and M-CFC numbers were low within granulomas. Circulating CSF-1 levels were elevated, but the vigorous granuloma-secreted CSF-1 level was low. During the chronic phase of the infection, the number of GM-CFC within the bone marrow and levels of circulating CSF-1 returned to normal. Conversely, a sharp increase in the number of M-CFC occurred within the small immunomodulated granulomas that also secreted high levels of CSF-1. The frequency of M-CFC that proliferated under exogenously added CSF-1 within the immunomodulated granulomas was significantly higher than that of cells in the vigorous granulomas. Adherent macrophage-rich cells obtained after dispersal of the granulomas appeared to be one source of CSF-1 production. These data indicate that during the infection the macrophage supply to and replicative ability within the granulomas is influenced by systemically and/or locally produced CSF-1.