Karnovsky M L, Bishop A, Camerero V C, Paz M A, Colepicolo P, Ribeiro J M, Gallop P M
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 26506-9223.
Environ Health Perspect. 1994 Dec;102 Suppl 10(Suppl 10):43-4. doi: 10.1289/ehp.94102s1043.
Although great progress has been made in understanding the respiratory burst of leukocytes that produce superoxide (O2-), it is possible that a component or components, might have been overlooked. Furthermore, O2- production and its sequels, though cardinal in bactericidal action, might ultimately be damaging to the host's own cells. It is important, therefore, that a biologic mechanism exist to turn off O2- production by stimulated leukocytes. This article offers evidence that methoxatin (PQQ), a redox-cycling orthoquinone, might be involved in O2- production by leukocytes. This is based on the fact that inhibitors of O2- production, such as diphenylene iodonium (DPI) and 4,5-dimethylphenylene diamine (DIMPDA), were shown to sequester PQQ in leukocytes, i.e., to form adducts with that substance. Addition of PQQ to cells blocked with the inhibitors partially restored O2- release. With respect to turning off cellular O2- release, a factor was observed to be released to the medium by old macrophages (14 days old, but not by those less than 7 days old). Such conditioned medium, when added to stimulated neutrophils or macrophages, blocked O2- release. This factor was sensitive to proteases, exhibited molecular sizes of 3 and 11 kDa, and its action was independent of the nature of the stimulus applied to the leukocytes. It was partially purified by column (sizing) chromatography and HPLC. It seems to be a general modulator of the release of reactive oxygen species by phagocytes and is irrespective of phagocytic cellular type, or species from which the cells were derived.
尽管在理解产生超氧化物（O2-）的白细胞呼吸爆发方面已经取得了很大进展，但仍有可能一个或多个组成部分被忽视了。此外，O2-的产生及其后续反应虽然在杀菌作用中至关重要，但最终可能对宿主自身的细胞造成损害。因此，存在一种生物学机制来关闭受刺激白细胞的O2-产生非常重要。本文提供了证据表明，氧化还原循环邻醌甲氧基黄素（PQQ）可能参与白细胞产生O2-的过程。这是基于以下事实：O2-产生的抑制剂，如二苯基碘鎓（DPI）和4,5-二甲基苯二胺（DIMPDA），被证明能在白细胞中螯合PQQ，即与该物质形成加合物。向用抑制剂阻断的细胞中添加PQQ可部分恢复O2-的释放。关于关闭细胞O2-释放，观察到一种因子由老龄巨噬细胞（14天龄，但7天龄以下的巨噬细胞不释放）释放到培养基中。这种条件培养基添加到受刺激的中性粒细胞或巨噬细胞中时，可阻断O2-释放。该因子对蛋白酶敏感，分子大小为3 kDa和11 kDa，其作用与施加于白细胞的刺激性质无关。它通过柱（分子筛）色谱法和高效液相色谱法进行了部分纯化。它似乎是吞噬细胞释放活性氧的一种普遍调节剂，与吞噬细胞类型或细胞来源的物种无关。
