The roles of degranulation and superoxide anion generation in neutrophil aggregation.
The roles of degranulation and superoxide anion generation in neutrophil aggregation.
复制标题
脱颗粒和超氧阴离子生成在中性粒细胞聚集中的作用。
DOI：
10.1016/0167-4889(82)90023-4
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Weissmann,G
中科院分区：
文献类型：
--
作者：
Kaplan,HB;Edelson,HS;Friedman,R;Weissmann,G
人中性粒细胞在适当的刺激下聚集，产生O β 2并分泌溶酶体成分。为了确定这些反应之间是否存在因果关系，中性粒细胞暴露于N-甲酰-甲硫氨酰-亮氨酰-苯丙氨酸、佛波醇肉豆蔻酸酯或两种钙离子载体A23187和前列腺素Bx。每个代理人都引起了上述所有反应。引起30·106中性粒细胞/ml聚集所需的浓度与产生O 2或释放溶菌酶所需的浓度相当。在一系列旨在分离这些反应的实验中，将细胞悬浮在太稀的浓度（3·106中性粒细胞/ml）中，以允许发生聚集，O β 2产生和溶菌酶释放是可测量的，并且以剂量依赖性方式随刺激浓度而变化。在第二系列实验中，用4，4 ′-二异硫氰基芪-2，2 ′-二磺酸处理中性粒细胞，以抑制脱粒，而不影响O β 2生成。聚集被抑制在一个平行的方式与溶菌酶释放。用超氧化物歧化酶和过氧化氢酶去除培养基中可检测到的O_（12）后，聚集和溶菌酶释放不受影响，表明聚集不是由于胞外培养基中存在O_（12）或其产物所致。无论是静息细胞的聚集，也没有增强fMet-Leu-Phe诱导的聚集时，观察细胞暴露于脱颗粒的中性粒细胞或成分的特定颗粒（溶菌酶，乳铁蛋白）的上清液。动力学分析表明，在细胞松弛素B的情况下，脱粒前聚集，而在其存在下，聚集前脱粒。
Human neutrophils when exposed to appropriate stimuli aggregate, generate O⨪2and secrete lysosomal constituents. To determine whether a causal relationship may exist between these responses neutrophils were exposed to eitherN-formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, or the two calcium ionophores, A23187 and prostaglandin Bx. Each agent elicited all of the above responses. The concentrations required to elicit the aggregation of 30·106neutrophils/ml were comparable to that required for O⨪2generation or lysozyme release. In a series of experiments designed to dissociate these responses, cells were suspended in a concentration too dilute (3·106neutrophils/ml) to permit aggregation to occur, O⨪2generation and lysozyme release was measurable and varied in a dose-dependent fashion to the concentration of stimulus. In a second series of experiments, neutrophils were treated with 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid to inhibit degranulation without affecting O⨪2generation. Aggregation was inhibited in a parallel fashion with lysozyme release. When detectable O⨪2was removed from the medium by superoxide dismutase and catalase, aggregation and lysozyme release proceeded unaffected showing that aggregation can not be due to the presence of O⨪2or its products in the extracellular medium. Neither aggregation of resting cells nor augmentation of fMet-Leu-Phe-induced aggregation was observed when cells were exposed to either supernatants of degranulated neutrophils or constituents of specific granules (lysozyme, lactoferrin). Kinetic analysis showed that in the absence of cytochalasin B degranulation preceded aggregation, while in its presence aggregation preceded degranulation.