Effects of retinoic acid on the activation and fusion of mouse alveolar macrophages induced by 1α,25‐dihydroxyvitamin D 3

1α, 25‐dihydroxyvitamin D 3 [1α,25(OH) 2 D 3 ] directly induces both fusion and cytotoxicity in murine alveolar macrophages. Unlike 1α,25(OH) 2 D 3 , retinoic acid per se did not induce fusion of alveolar macrophages, but it greatly enhanced the 1α,25(OH) 2 D 3 ‐induced fusion every time the macrophages were treated simultaneously with the two vitamins. The giant cells induced by the two vitamins were much larger than those induced by 1α,25(OH) 2 D 3 alone. The macrophages treated with 1α,25(OH) 2 D 3 started to fuse 36 h after the addition of the vitamin, whereas the macrophages pretreated with retinoic acid for 24 h began to fuse immediately after 1α,25(OH) 2 D 3 was added. 1α,25(OH) 2 D 3 and retinoic acid activated alveolar macrophages similarly, measured by the enhancement of glucose consumption and the induction of cytotoxicity against tumor cells, though 1α,25(OH) 2 D 3 was 100 times more potent than retinoic acid on a molar basis. Simultaneous treatment with physiological concentrations of 1α,25(OH) 2 D 3 (0.12 n M ) and retinoic acid (10 n M ) induced cytotoxicity additively. Morphological examinations revealed that the treated cells were enlarged and flattened with numerous filopodia. These results clearly indicate that both 1α,25(OH) 2 D 3 and retinoic acid similarly activate alveolar macrophages, and the activated state is prerequisite to the fusion of macrophages induced by 1α,25(OH) 2 D 3 .