Di Mauro C, Cavalli G, Curzio M, Ferretti C, Mengozzi G, Rossi M A, Paradisi L, Dianzani M U
Department of Medicine and Experimental Oncology, University of Turin, Italy.
Int J Tissue React. 1995;17(2):61-72.
The peroxidative breakdown of membrane polyunsaturated fatty acids leads to the production of various carbonylic compounds: among these, 4-hydroxynonenal (HNE) displays many biological properties related to neutrophil functions. It stimulates rat and human polymorphonuclear (PMN) cell migration and has been detected during inflammation. The aim of this study was to elucidate and well characterize the mechanism of action of HNE. We observed that micromolar HNE concentrations that influence migration do not stimulate differently from many other chemoattractants the human PMN chemiluminescence (CL) induced by opsonized zymosan or phorbol 12-myristate 13-acetate (PMA). Higher HNE concentrations inhibit the light emission of stimulated PMN. Addition of 0.5 mM L-arginine (L-arg), the substrate of nitric oxide synthase, into the incubation medium had the effect of modifying human CL. In fact, HNE at 10-6 M, a concentration which is ineffective in absence of L-Arg, at 10-5 M reduces CL emission of PMA-stimulated human PMN. These observations have been confirmed by electron-spin resonance (ESR) analysis. HNE, according to other stimuli, induced PMN phosphoinositide-specific phospholipase C (PL-C). All these results considered together suggest the conclusion that HNE represents an interesting endogenous molecule that plays a role as an inflammatory mediator involved a) in the recruitment of phagocytic cells at the inflamed area, and b) in the modulation of respiratory burst and of nitric oxide (NO) production.
其中，4-羟基壬烯醛（HNE）具有许多与中性粒细胞功能相关的生物学特性。它能刺激大鼠和人类多形核（PMN）细胞迁移，并且在炎症过程中被检测到。本研究的目的是阐明并充分表征HNE的作用机制。我们观察到，影响迁移的微摩尔浓度的HNE与许多其他趋化因子对经调理酵母聚糖或佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）诱导的人类PMN化学发光（CL）的刺激作用并无差异。更高浓度的HNE会抑制受刺激PMN的发光。向孵育培养基中添加0.5 mM一氧化氮合酶的底物L-精氨酸（L-arg）具有改变人类CL的作用。事实上，在不存在L-Arg时无作用的10⁻⁶ M浓度的HNE，在10⁻⁵ M时会降低PMA刺激的人类PMN的CL发射。这些观察结果已通过电子自旋共振（ESR）分析得到证实。与其他刺激一样，HNE诱导PMN磷酸肌醇特异性磷脂酶C（PL-C）。综合所有这些结果表明，HNE是一种有趣的内源性分子，它作为一种炎症介质发挥作用，a）参与炎症部位吞噬细胞的募集，b）参与呼吸爆发和一氧化氮（NO）产生的调节。
