Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China.
Biochem Biophys Res Commun. 2013 Jan 11;430(2):816-21. doi: 10.1016/j.bbrc.2012.11.063. Epub 2012 Dec 5.
Tissue penetration of neutrophils is a key process in many inflammatory diseases. In response to inflammatory stimuli such as N-formyl-methionine-leucine-phenylalanine (fMLP), neutrophils polarize and migrate towards the chemotactic gradient of the stimulus. Elevated intracellular Ca(2+) concentration is known to play a critical role in neutrophil polarization and migration; however, the exact mechanism remains elusive. Here, we demonstrated that fMLP stimulation caused not only store-operated calcium entry (SOCE), but also receptor-operated calcium entry (ROCE) in neutrophils by using both pharmacological and neutralizing monoclonal antibody approaches. We also investigated neither Rac2 nor Cdc42 activation could take place if either SOCE or ROCE was inhibited. This study thus provides the first evidence for coordination of Ca(2+) influx by SOCE and ROCE to regulate neutrophil polarization.
中性粒细胞向组织内的迁移是许多炎症性疾病的一个关键过程。在诸如 N-甲酰基-甲硫氨酸-亮氨酸-苯丙氨酸（fMLP）等炎症刺激物的作用下，中性粒细胞发生极化并向刺激物的趋化梯度方向迁移。已知细胞内 Ca2+浓度的升高在中性粒细胞的极化和迁移中起着关键作用；然而，确切的机制仍不清楚。在这里，我们通过药理学和中和单克隆抗体的方法证明，fMLP 刺激不仅引起了钙库操纵性钙内流（SOCE），而且引起了受体操纵性钙内流（ROCE）。我们还发现，如果抑制 SOCE 或 ROCE，Rac2 或 Cdc42 的激活都不会发生。因此，本研究首次提供了证据表明，SOCE 和 ROCE 协调钙内流来调节中性粒细胞的极化。
