Walters J D, Cario A C, Danne M M, Marucha P T
Section of Periodontology, College of Dentistry, Ohio State University Health Sciences Center, Columbus 43210, USA.
J Inflamm. 1998;48(1):40-6.
Tumor necrosis factor-alpha (TNF-alpha) induces a rapid increase in polymorphonuclear leukocyte (PMN) polyamine content which appears to be required for optimal priming of the respiratory burst. The objective of the present study was to determine whether inhibition of polyamine biosynthesis modifies PMN responses to lipopolysaccharide (LPS), granulocyte-macrophage colony-stimulating factor (GM-CSF), or granulocyte colony-stimulating factor (G-CSF). Treatment with alpha-difluoromethylornithine (DFMO), a selective inhibitor of the rate-limiting biosynthetic enzyme ornithine decarboxylase, produced dose-dependent inhibition of the respiratory burst in PMNs that were primed by these agents and subsequently activated by formyl-Met-Leu-Phe (fMLP). However, DFMO did not significantly inhibit fMLP-stimulated superoxide generation or alter the induction of PMN adhesion and interleukin-1 beta (IL-1 beta) mRNA expression by LPS or GM-CSF. Antagonism of priming by DFMO correlated with a dose-dependent attenuation of fMLP-induced intracellular Ca2+ mobilization (r > or = 0.96). Since Ca2+ plays an important role in modulating the respiratory burst in primed PMNs, this could, in part, account for the selective effects of DFMO.
肿瘤坏死因子-α（TNF-α）可使多形核白细胞（PMN）中的多胺含量迅速增加，这似乎是呼吸爆发最佳启动所必需的。本研究的目的是确定多胺生物合成的抑制是否会改变PMN对脂多糖（LPS）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）或粒细胞集落刺激因子（G-CSF）的反应。用α-二氟甲基鸟氨酸（DFMO）（一种限速生物合成酶鸟氨酸脱羧酶的选择性抑制剂）处理，可对由这些因子启动并随后被甲酰甲硫氨酸-亮氨酸-苯丙氨酸（fMLP）激活的PMN中的呼吸爆发产生剂量依赖性抑制。然而，DFMO并未显著抑制fMLP刺激的超氧化物生成，也未改变LPS或GM-CSF诱导的PMN黏附及白细胞介素-1β（IL-1β）mRNA表达。DFMO对启动的拮抗作用与fMLP诱导的细胞内Ca2+动员的剂量依赖性减弱相关（r≥0.96）。由于Ca2+在调节已启动的PMN的呼吸爆发中起重要作用，这可能部分解释了DFMO的选择性作用。
