Generation of nitrogen-chlorine oxidants by human phagocytes.
Generation of nitrogen-chlorine oxidants by human phagocytes.
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人类吞噬细胞产生氮氯氧化剂。
DOI：
10.1172/jci111544
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Weiss,SJ
中科院分区：
文献类型：
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作者：
Test,ST;Lampert,MB;Ossanna,PJ;Thoene,JG;Weiss,SJ
人类吞噬细胞可以被触发产生大量的长寿命的氮氯衍生物。这类氧化剂可以在加入佛波醇肉豆蔻酸酯乙酸酯或调理的酵母聚糖颗粒后5分钟检测到。与已知由吞噬细胞产生的所有其他氧代谢产物不同，在刺激后90分钟，可以在细胞上清液中容易地检测到氮-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下有利，并被超生理浓度的碘化物或溴化物抑制。氧化剂本质上是亲水性的，并且具有在37 ° C下5小时至在4 ° C下大于100小时的范围内的半衰期。累积的氮-氯衍生物的凝胶过滤色谱显示，由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Mr范围为150- 5，000。一半的氮氯衍生物迁移作为一个单峰，约150的先生。该馏分的氨基酸分析鉴定出β-氨基酸牛磺酸为存在的单一含氮化合物。在血清白蛋白的存在下触发的中性粒细胞积累的氮-氯衍生物的量增加，同时继续产生其内源性低先生氧化剂。36 Cl掺入的定量分析表明，白蛋白分子被氯化，形成氮-氯和碳-氯键。我们的结论是，人类吞噬细胞可以氯化内源性和外源性含氮化合物在炎症部位产生的氮氯衍生物的异质混合物。吞噬细胞产生这类长寿命氧化剂的能力，其亲水特性限制了其定位于细胞外空间，表明这些物种在调节炎症反应中起重要作用。
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.