Effect of amiodarone on cytokine release and on enzyme activities of mouse alveolar macrophages, bone marrow macrophages, and blood monocytes.
The effect off amiodarone, a cationic amphiphilic drug, on cytokine release from, and on protein kinase C (PKC) activity of, mouse alveolar macrophages, bone marrow macrophages, and blood monocytes was examined. In addition, its effect on three enzymes in these cells was also determined. Amiodarone suppressed the growth of all cell types at high doses. As regards cytokine release, amiodarone caused an increase in interleukin-1 (IL-1) alpha, IL-1 beta, and tumor necrosis factor (TNF) alpha release from alveolar macrophages but not from marrow macrophages and monocytes. PKC activity was increased by amiodarone only in alveolar macrophages. And the treatment with amiodarone severely suppressed the H(+)-ATPase, sphingomyelinase, and phospholipase A2 activities in alveolar macrophages. But these enzyme activities in bone marrow macrophages and monocytes were not suppressed so much as in alveolar macrophages. This current study indicated that mouse alveolar macrophages treated with amiodarone undergo suppression of H(+)-ATPase, resulting in suppression of sphingomyelinase and phospholipase A2 activity, and in activation of PKC activity and release of cytokines. It also showed that changes in activities of all three enzymes in alveolar macrophages are different from those in bone marrow macrophages and monocytes with respect to reactivity toward amiodarone.
Futamura
Y
Y
Department of Pharmacology, Toho University School of Medicine, Tokyo, Japan.
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D013108:Sphingomyelin Phosphodiesterase; D006180:Proton-Translocating ATPases; D000638:Amiodarone