NEUTROPHIL DE-GRANULATION INHIBITS POTENTIAL HYDROXYL-RADICAL FORMATION - RELATIVE IMPACT OF MYELOPEROXIDASE AND LACTOFERRIN RELEASE ON HYDROXYL-RADICAL PRODUCTION BY IRON-SUPPLEMENTED NEUTROPHILS ASSESSED BY SPIN-TRAPPING TECHNIQUES
NEUTROPHIL DE-GRANULATION INHIBITS POTENTIAL HYDROXYL-RADICAL FORMATION - RELATIVE IMPACT OF MYELOPEROXIDASE AND LACTOFERRIN RELEASE ON HYDROXYL-RADICAL PRODUCTION BY IRON-SUPPLEMENTED NEUTROPHILS ASSESSED BY SPIN-TRAPPING TECHNIQUES
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DOI：
10.1042/bj2640447
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发表时间：
1989-12-01
影响因子：
4.1
通讯作者：
COHEN, MS
中科院分区：
文献类型：
--
作者：
BRITIGAN, BE;HASSETT, DJ;COHEN, MS
中性粒细胞在体外形成羟基自由基（.OH）需要外源铁。最近的两项研究 [Britigan、Rosen、Thompson、Chai 和 Cohen (1986) J. Biol。化学。 261、17026-17032；温特伯恩 (1987) J. Clin。投资。 [78, 545-550] 均报道中性粒细胞脱颗粒可能会抑制 .OH 的形成，但对于负责因素髓过氧化物酶 (MPO) 或乳铁蛋白 (LF) 的结论不同。通过使用先前开发的自旋捕获系统，可以对超氧阴离子 (O2-) 和 .OH 产生进行特定的在线检测，比较了 MPO 和 LF 释放对中性粒细胞 .OH 产生的影响。当用佛波醇肉豆蔻酸酯乙酸酯或调理的酵母聚糖刺激补充铁-二亚乙基三胺五乙酸的中性粒细胞时，发生·OH形成，但尽管持续产生O 2 - ，但过早终止。叠氮化物对 MPO 的抑制增加了 .OH 形成的程度，但没有增加其持续时间。当使用 MPO 缺陷的中性粒细胞时，没有发现叠氮化物效应。抗 LF 抗体增加了 .OH 生成的幅度和持续时间。用细胞松弛素 B 预处理中性粒细胞以防止吞噬体形成，并没有改变叠氮化物或抗 LF 对中性粒细胞 .OH 产生的相对影响。叠氮化物或抗 LF 对自旋捕获加合物稳定性的影响作为混杂因素被消除。这些数据表明嗜中性粒细胞具有两种限制.OH产生的机制。 讨论了中性粒细胞衍生的氧化损伤的影响。
Hydroxyl radical (.OH) formation by neutrophils in vitro requires exogenous iron. Two recent studies [Britigan, Rosen, Thompson, Chai and Cohen (1986) J. Biol. Chem. 261, 17026-17032; Winterbourn (1987) J. Clin. Invest. 78, 545-550] both reported that neutrophil degranulation could potentially inhibit the formation of .OH, but differed in their conclusions as to the responsible factor, myeloperoxidase (MPO) or lactoferrin (LF). By using a previously developed spin-trapping system which allows specific on-line detection of superoxide anion (O2-) and .OH production, the impact of MPO and LF release on neutrophil .OH production was compared. When iron-diethylenetriaminepenta-acetic acid-supplemented neutrophils were stimulated with phorbol myristate acetate or opsonized zymosan, .OH formation occurred, but terminated prematurely in spite of continued O2- generation. Inhibition of MPO by azide increased the magnitude, but not the duration, of .OH formation. No azide effect was noted when MPO-deficient neutrophils were used. Anti-LF antibody increased both the magnitude and duration of .OH generation. Pretreatment of neutrophils with cytochalasin B to prevent phagosome formation did not alter the relative impact of azide or anti-LF on neutrophil .OH production. An effect of azide or anti-LF on spin-trapped-adduct stability was eliminated as a confounding factor. These data indicate that neutrophils possess two mechanisms for limiting .OH production. Implications for neutrophil-derived oxidant damage are discussed.