1 alpha,25-dihydroxyvitamin D3 promotes fusion of mouse alveolar macrophages both by a direct mechanism and by a spleen cell-mediated indirect mechanism.

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Abstract
Extensive fusion was induced in mouse alveolar macrophages by treatment with conditioned media obtained from spleen cell cultures treated with 15 .mu.g of phytohemagglutinin or concanavalin A/ml or with 12 nM 1.alpha.,25-dihydroxyvitamin D3 [1.alpha.,25(OH2)D3]. The fusion rate was 80-90% on day 3. In addition, 1.alpha.,25(OH)2D3 added directly to alveolar macrophages induced fusion of about 35% of the cells on days 3, whereas direct addition of phytohemagglutinin and concanavalin A did not enhance fusion at all. When conditioned media from spleen cell or T cell cultures treated with 12 nM 1.alpha.,25(OH)2D3 were applied to a Sephadex G-100 column, a fusion factor (MW 37,000-70,000) could be separated from 1.alpha.,25(OH)2D3. 1.alpha.,25(OH)2D3 induced fusion at 0.012-120 nM in a dose-dependent manner both by direct action and by spleen cell-mediated indirect action, but the fusion rate was always much greater in the latter than in the former at each concentration of the vitamin. Of the vitamin D3 derivatives tested, 1.alpha.,25(OH)2D3 was the most potent, followed successively by 1.alpha.,24R,25-trihydroxyvitamin D3, 1.alpha.-hydroxyvitamin D3, 25-hydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3. 1.alpha.,25(OH)2D3 induces fusion of mouse alveolar macrophages by both a direct and an indirect mechanism, the latter mediated by spleen cells, probably by T cells.