Regulation of neutrophil inflammatory mediator release: chemotactic peptide activation of stimulus-dependent cytotoxicity.
Regulation of neutrophil inflammatory mediator release: chemotactic peptide activation of stimulus-dependent cytotoxicity.
复制标题
中性粒细胞炎症介质释放的调节：刺激依赖性细胞毒性的趋化肽激活。
DOI：
10.4049/jimmunol.130.2.850
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发表时间：
1983
影响因子：
4.4
通讯作者：
J. Lukens
中科院分区：
文献类型：
--
作者：
D. English;J. Lukens
人中性粒细胞刺激佛波醇肉豆蔻酸酯乙酸酯（PMA）能够损害人红白血病K-562靶细胞的3小时51铬释放试验评估。来自儿童慢性肉芽肿病患者的中性粒细胞在介导PMA刺激的细胞溶解中无效。细胞毒性在厌氧条件下以及过氧化氢酶和几种自由基清除剂抑制。超氧化物歧化酶、叠氮化物和氰化物未能抑制PMA依赖的细胞毒性。研究了趋化肽N-甲酰-甲硫氨酰-亮氨酰-苯丙氨酸（FMLP）对刺激依赖性细胞毒性的影响。用1.0 × 10（-7）M FMLP预孵育的中性粒细胞没有显示出增加的细胞毒性反应，但加入PMA后，其产生细胞毒性的能力明显增强。PMA刺激的细胞毒性增强是由于对FMLP的可逆细胞反应。细胞毒性反应的动力学反映了趋化肽处理的中性粒细胞释放细胞毒性介质的可能性，以更大的程度和更快的速度比未处理的中性粒细胞。虽然叠氮化物和超氧化物歧化酶没有抑制趋化肽激活的中性粒细胞的细胞毒性反应，反应被阻止过氧化氢酶和几种自由基清除剂显着抑制。FMLP增强细胞毒性反应的能力与其在各种条件下增强PMA刺激的化学发光密切相关。此外，PMA刺激的中性粒细胞介导二甲基亚砜产生甲烷和α-酮-γ-甲硫基-丁酸（KMB）产生乙烯的能力-定量氧化自由基产生的测定-如果中性粒细胞与FMLP预孵育，则增加。这些结果表明，一个趋化因子大大增强释放细胞毒性介质从中性粒细胞刺激后，与非趋化剂。细胞毒性介质似乎是氧化代谢的产物。对趋化性刺激作出反应以到达炎症部位的中性粒细胞的细胞毒性潜力可以以类似的方式被激活。
Human neutrophils stimulated with phorbol myristate acetate (PMA) were able to damage human erythroleukemic K-562 target cells as assessed by a 3-hr 51Cr-release assay. Neutrophils from a patient with chronic granulomatous disease of childhood were ineffective in mediating PMA-stimulated cytolysis. Cytotoxicity was inhibited under anaerobic conditions as well as by catalase and several free radical scavengers. Superoxide dismutase, azide, and cyanide failed to inhibit PMA-dependent cytotoxicity. The influence of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) on stimulus-dependent cytotoxicity was examined. Neutrophils preincubated with 1.0 X 10(-7) M FMLP did not display an increased cytotoxic response, but were markedly amplified in their ability to effect cytotoxicity with the addition of PMA. Enhancement of PMA-stimulated cytotoxicity resulted from a reversible cellular response to FMLP. The kinetics of the cytotoxic responses reflected the possibility that chemotactic peptide-treated neutrophils released cytotoxic mediators to a greater extent and at a faster rate than did untreated neutrophils. Although azide and superoxide dismutase did not inhibit cytotoxic responses of chemotactic peptide-activated neutrophils, the response was prevented by catalase and was markedly inhibited by several free radical scavengers. The ability of FMLP to enhance cytotoxic responses correlated well with its enhancement of PMA-stimulated chemiluminescence under a variety of conditions. In addition, the ability of PMA-stimulated neutrophils to mediate methane generation from dimethyl sulfoxide and ethylene generation from alpha keto-gamma-methiol-butyric acid (KMB)--assays that quantitate the generation of oxidizing radicals--was increased if the neutrophils were preincubated with FMLP. These results demonstrate that a chemotactic factor greatly potentiates the release of cytotoxic mediators from neutrophils upon stimulation with a nonchemotactic agent. The cytotoxic mediators appear to be products of oxidative metabolism. The cytotoxic potential of neutrophils that have responded to chemotactic stimuli to reach sites of inflammation may be activated in a similar manner.