The relationship between fusion and proliferation in mouse alveolar macrophages

We have reported that protein factors separated from conditioned media of Concanavalin A-stimulated spleen cell cultures induce growth and fusion of mouse alveolar macrophages. A macrophages growth factor (MGF) was purified and, at the final step of purification on HPLC, eluted at the same position as a colony-stimulating factor (CSF), suggesting that MGF is identical with CSF. In the present study, we examined the relationship between proliferation and fusion of macrophages using purified CSF (MGF) and 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3]. The latter was used in place of a macrophage fusion factor which is supposed to be contained in the same conditioned medium, since a macrophage fusion factor has not yet been isolated. Adding less than 5% unfractionated conditioned medium from Concanavalin A-stimulated spleen cells markedly induced proliferation of alveolar macrophages without inducing fusion. In contrast, adding the same unfractionated conditioned medium at concentrations of 10% or more suppressed proliferation dose dependently, whereas it induced fusion reciprocally. Proliferation of macrophages was similarly enhanced by adding purified CSF or retinoic acid. Fusion of macrophages was induced by 1 alpha,25-(OH)2D3, but not by purified CSF or retinoic acid. Adding 1 alpha,25-(OH)2D3 together with purified CSF or retinoic acid completely suppressed the increase of proliferation induced by either growth factor, whereas that treatment rather potentiated the fusion induced by 1 alpha,25-(OH)2D3 alone. These results indicate that the fusion and proliferation of macrophages occur in a reciprocal fashion.