PMID- 3140603 OWN - NLM STAT- MEDLINE DCOM- 19881115 LR - 20131121 IS - 0884-0431 (Print) IS - 0884-0431 (Linking) VI - 1 IP - 2 DP - 1986 Apr TI - Polyamines are involved in the 1-alpha,25-dihydroxyvitamin D3-induced fusion of mouse alveolar macrophages. PG - 235-42 AB - We have reported that 1-alpha,25-dihydroxyvitamin D3 [1-alpha,25-(OH)2D3] directly induces fusion of mouse alveolar macrophages at a very high rate (circa 70-80%) by a mechanism involving protein synthesis (Proc. Natl. Acad. Sci. USA 80:5583, 1983; FEBS Letters 174:61, 1984). While examining further the mechanism of the 1-alpha,25-(OH)2D3-induced fusion of macrophages, we found that polyamines are involved in this mechanism. Mouse alveolar macrophages incubated with 12 nM 1-alpha,25-(OH)2D3 began to fuse at 36 h and the fusion rate increased linearly up to 60 h. Addition of as much as 0.05-5 mM alpha-difluoromethylornithine (alpha-DFMO), a specific inhibitor of ornithine decarboxylase, did not inhibit fusion appreciably, but addition of 0.05-5 microM methylglyoxal bis(guanylhydrazone) (MGBG), an inhibitor of S-adenosylmethionine decarboxylase, strikingly inhibited fusion. When macrophages were treated with both 12 nM 1-alpha,25-(OH)2D3 and 5 microM MGBG for the first 12 h and incubated further for 60 h in fresh medium containing 1-alpha,25-(OH)2D3, fusion was significantly inhibited, suggesting that the 1-alpha,25-(OH)2D3-induced synthesis of polyamines precedes fusion. The inhibition by MGBG of the 1-alpha,25-(OH)2D3-induced fusion was restored completely by adding 1 microM spermidine or spermine or 100 microM putrescine. None of the polyamines alone induced fusion. MGBG suppressed the 1-alpha,25-(OH)2D3-induced incorporation of [3H]-leucine into the trichloroacetic acid-insoluble fraction in macrophages, but its inhibitory effect was restored completely by adding 1 microM spermidine.(ABSTRACT TRUNCATED AT 250 WORDS) FAU - Hayashi, T AU - Hayashi T AD - Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan. FAU - Shinki, T AU - Shinki T FAU - Tanaka, H AU - Tanaka H FAU - Abe, E AU - Abe E FAU - Suda, T AU - Suda T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Bone Miner Res JT - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JID - 8610640 RN - 0 (Polyamines) RN - 2FZ7Y3VOQX (Spermine) RN - FXC9231JVH (Calcitriol) RN - OD5Q0L447W (Mitoguazone) RN - U87FK77H25 (Spermidine) RN - ZQN1G5V6SR (Eflornithine) SB - IM MH - Animals MH - Calcitriol/*pharmacology MH - Cell Fusion/drug effects MH - Cells, Cultured MH - Eflornithine/pharmacology MH - Macrophages/*drug effects MH - Male MH - Mice MH - Mitoguazone/pharmacology MH - Polyamines/*pharmacology MH - Protein Biosynthesis MH - Pulmonary Alveoli/cytology/*drug effects MH - Spermidine/pharmacology MH - Spermine/pharmacology EDAT- 1986/04/01 00:00 MHDA- 1986/04/01 00:01 CRDT- 1986/04/01 00:00 PHST- 1986/04/01 00:00 [pubmed] PHST- 1986/04/01 00:01 [medline] PHST- 1986/04/01 00:00 [entrez] AID - 10.1002/jbmr.5650010211 [doi] PST - ppublish SO - J Bone Miner Res. 1986 Apr;1(2):235-42. doi: 10.1002/jbmr.5650010211.