Desensitization of calcium mobilization and cell function in human neutrophils.
Desensitization of calcium mobilization and cell function in human neutrophils.
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人类中性粒细胞中钙动员和细胞功能的脱敏。
DOI：
10.1042/bj2620165
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Lad,PM
中科院分区：
文献类型：
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作者：
Lee,GH;Kaptein,JS;Scott,SJ;Niedzin,H;Kalunta,CI;Lad,PM
用化学引诱物甲酰甲硫氨酰-亮氨酰-苯丙氨酸预处理的中性粒细胞在再次暴露于相同配体时变得无反应，这一过程称为脱敏。我们已经研究了是否脱敏的转导（Ca 2+动员）或其他细胞功能（超氧化物生成，酶释放，或聚集）同步发生。通过使用Fura-2加载的细胞的Ca 2+动员和聚集的同时研究表明，在聚集反应被废除的条件下，大部分的Ca 2+动员是不变的。然后进行进一步的研究，以确定是否脱敏的Ca 2+动员实际上可以被诱导。观察到脱敏，并且依赖于细胞暴露于配体的次数、配体的浓度以及配体是否留在培养基中或被去除。再敏感化的模式取决于实验设计。在配体连续存在的条件下，在随后的挑战中未观察到Ca 2+动员反应的恢复。相反，在去除配体时，该响应显示部分恢复。而完全脱敏的聚集注意到，酶的释放表现出显着程度较低的脱敏，并需要更频繁的曝光之前，它被观察到的配体。很少或没有观察到超氧化物生成的脱敏，无论使用的条件。以佛波醇肉豆蔻酸酯为配体的研究表明，它能同时抑制Ca 2+的动员和聚集。我们的研究结果表明，在人类中性粒细胞的脱敏离散机制是可能的，一个特定的功能（聚集）的脱敏并不意味着其他功能的伴随脱敏。
Neutrophils pretreated with the chemoattractant formylmethionyl-leucyl-phenylalanine become unresponsive when re-exposed to the same ligand, a process termed desensitization. We have examined whether desensitization of transduction (Ca2+ mobilization) or of other cell functions (superoxide generation, enzyme release, or aggregation) occurs synchronously. Simultaneous studies of Ca2+ mobilization and aggregation by using Fura-2-loaded cells indicate that, under conditions where the aggregation response is abolished, most of the Ca2+ mobilization is unaltered. Further studies were then carried out to ascertain whether desensitization of Ca2+ mobilization could in fact be induced. Desensitization was observed, and was dependent on the number of exposures of the cells to the ligand, the concentration of the ligand, and whether the ligand was left in the medium or was removed. The pattern of resensitization was dependent on the experimental design. Under conditions where ligand was continuously present, no recovery of the Ca2+-mobilization response was seen with subsequent challenges. In contrast, on removal of ligand, this response showed partial recovery. Whereas complete desensitization of aggregation was noted, enzyme release showed a markedly lesser degree of desensitization and required more frequent exposures to the ligand before it was observed. Little or no desensitization of superoxide generation was observed regardless of the conditions utilized. Studies using phorbol myristate acetate as the ligand showed that Ca2+ mobilization and aggregation could be simultaneously inhibited. Our results suggest that discrete mechanisms of desensitization are possible in human neutrophils, and that desensitization of one particular function (aggregation) does not imply concomitant desensitization of other functions.