Effects of retinoic acid on the activation and fusion of mouse alveolar macrophages induced by 1α,25-dihydroxyvitamin D3

Open Access
Publisher Website
Google Scholar
Abstract
1α, 25-dihydroxyvitamin D3 [1α,25(OH)2D3] directly induces both fusion and cytotoxicity in murine alveolar macrophages. Unlike 1α,25(OH)2D3, retinoic acid per se did not induce fusion of alveolar macrophages, but it greatly enhanced the 1α,25(OH)2D3-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)2D3 alone. The macrophages treated with 1α,25(OH)2D3 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)2D3 was added. 1α,25(OH)2D3 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)2D3 was 100 times more potent than retinoic acid on a molar basis. Simultaneous treatment with physiological concentrations of 1α,25(OH)2D3 (0.12 nM) and retinoic acid (10 nM) 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)2D3 and retinoic acid similarly activate alveolar macrophages, and the activated state is prerequisite to the fusion of macrophages induced by 1α,25(OH)2D3.
Funding Information
  • Ministry of Sciences, Education and Culture of Japan (60771537, 60440086)

This publication has 16 references indexed in Scilit: