Calcium flux in neutrophils synchronizes β2 integrin adhesive and signaling events that guide inflammatory recruitment

被引:78
作者
Schaff, Ulrich Y. [1 ]
Yamayoshi, Itsukyo [1 ]
Tse, Tiffany [1 ]
Griffin, Donald [1 ]
Kibathi, Lilian [1 ]
Simon, Scott I. [1 ]
机构
[1] Univ Calif Davis, Dept Biomed Engn, Genome & Biomed Sci Facil, Davis, CA 95616 USA
关键词
neutrophils; shear stress; calcium signaling; integrin affinity;
D O I
10.1007/s10439-008-9453-8
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Intracellular calcium flux is an early step in the signaling cascade that bridges ligation of selectin and chemokine receptors to activation of adhesive and motile functions during recruitment on inflamed endothelium. Calcium flux was imaged in real time and provided a means of correlating signaling events in neutrophils rolling on E-selectin and stimulated by chemokine in a microfluidic chamber. Integrin dependent neutrophil arrest was triggered by E-selectin tethering and ligation of IL-8 seconds before a rapid rise in intracellular calcium, which was followed by the onset of pseudopod formation. Calcium flux on rolling neutrophils increased in a shear dependent manner, and served to link integrin adhesion and signaling of cytoskeletally driven cell polarization. Abolishing calcium influx through membrane expressed store operated calcium channels inhibited activation of high affinity beta(2) integrin and subsequent cell arrest. We conclude that calcium influx at the plasma membrane integrates chemotactic and adhesive signals, and functions to synchronize signaling of neutrophil arrest and migration in a shear stress dependent manner.
引用
收藏
页码:632 / 646
页数:15
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