Test S T, Lampert M B, Ossanna P J, Thoene J G, Weiss S J
J Clin Invest. 1984 Oct;74(4):1341-9. doi: 10.1172/JCI111544.
Human phagocytes can be triggered to generate large quantities of long-lived nitrogen-chlorine derivatives. This class of oxidants can be detected as early as 5 min after the addition of phorbol myristate acetate or opsonized zymosan particles. Unlike all other oxygen metabolites known to be generated by phagocytes, the nitrogen-chlorine compounds can be readily detected in cell supernatants 90 min after stimulation. The generation of these oxidants is linear with neutrophil concentration, favored at alkaline pH, and inhibited by supraphysiologic concentrations of iodide or bromide. The oxidants are hydrophilic in nature and have a half-life ranging from 5 h at 37 degrees C to greater than 100 h at 4 degrees C. Gel filtration chromatography of the accumulated nitrogen-chlorine derivatives revealed that the oxidants generated by neutrophils or monocytes are a complex mixture of products whose Mr range from 150-5,000. One-half of the nitrogen chlorine derivatives migrate as a single peak with an Mr of approximately 150. Amino acid analysis of this fraction identified the beta-amino acid, taurine, as the single nitrogenous compound present. Neutrophils triggered in the presence of serum albumin accumulated increased amounts of the nitrogen-chlorine derivatives while continuing to generate their endogenous low Mr oxidants. Quantitative analysis of the 36Cl incorporation revealed that the albumin molecule was chlorinated with the formation of both nitrogen-chlorine and carbon-chlorine bonds. We conclude that human phagocytes can chlorinate both endogenous and exogenous nitrogenous compounds at inflammatory sites to generate a heterogeneous mixture of nitrogen-chlorine derivatives. The ability of phagocytes to generate this class of long-lived oxidants whose hydrophilic characteristics restrict their localization to the extracellular space suggests that these species play an important role in modulating the inflammatory response.
人类吞噬细胞可被触发产生大量长寿的氮氯衍生物。早在添加佛波醇肉豆蔻酸酯乙酸盐或调理酵母聚糖颗粒后5分钟就能检测到这类氧化剂。与已知由吞噬细胞产生的所有其他氧代谢产物不同，刺激90分钟后可在细胞上清液中轻松检测到氮氯化合物。这些氧化剂的产生与中性粒细胞浓度呈线性关系，在碱性pH条件下更有利，且会被超生理浓度的碘化物或溴化物抑制。这些氧化剂本质上是亲水性的，半衰期在37℃时为5小时，在4℃时大于100小时。对积累的氮氯衍生物进行凝胶过滤色谱分析表明，中性粒细胞或单核细胞产生的氧化剂是一种复杂的产物混合物，其分子量范围为150 - 5000。一半的氮氯衍生物以单一峰的形式迁移，分子量约为150。对该部分进行氨基酸分析确定β - 氨基酸牛磺酸是唯一存在的含氮化合物。在血清白蛋白存在下被触发的中性粒细胞积累了更多的氮氯衍生物，同时继续产生其内源性低分子量氧化剂。对36Cl掺入量的定量分析表明，白蛋白分子被氯化，形成了氮氯键和碳氯键。我们得出结论，人类吞噬细胞可在炎症部位对内源性和外源性含氮化合物进行氯化，以产生氮氯衍生物的异质混合物。吞噬细胞产生这类长寿氧化剂的能力，其亲水性特征将它们限制在细胞外空间，这表明这些物质在调节炎症反应中起重要作用。
