Department of Bioengineering, University of Pennsylvania, 210 S 33rd St, Philadelphia, PA 19104, USA.
Integr Biol (Camb). 2014 Mar;6(3):348-56. doi: 10.1039/c3ib40225h. Epub 2014 Jan 31.
Neutrophils are mediators of innate immunity and motility is critical to their function. We used microcontact printing to investigate the relationship between density of adhesive ligands and the dynamics of neutrophil motility. We show that neutrophils adopt a well-spread morphology without a uropod on moderate densities of adhesion ligand. As density is increased, the morphology switches to a classic amoeboid shape. In addition to the morphological differences, the dynamics of motility were quantitatively distinct. Well-spread cells without uropods glide slowly with high persistence, while amoeboid cells made frequent directional changes migrating quickly with low persistence. Using an antibody panel against various integrin chains, we show that adhesion and motility on fibronectin are mediated by MAC-1 (αMβ2). The phenotypic switch could be generalized to other surface ligands, such as bovine serum albumin, to which the promiscuous MAC-1 also binds. These results suggest that neutrophils are capable of displaying multiple modes of motility as dictated by their adhesive environment.
中性粒细胞是先天免疫系统的介质,其运动能力对其功能至关重要。我们使用微接触印刷来研究黏附配体密度与中性粒细胞运动动力学之间的关系。我们发现,在中等密度的黏附配体上,中性粒细胞呈现出良好伸展的形态,没有尾足。随着密度的增加,形态转变为经典的阿米巴样形状。除了形态差异外,运动动力学也有明显的区别。没有尾足的伸展细胞缓慢滑行,具有高持久性,而快速迁移的阿米巴样细胞频繁改变方向,具有低持久性。使用针对各种整合素链的抗体面板,我们表明黏附素和运动性在纤维连接蛋白上是由 MAC-1(αMβ2)介导的。表型转换可以推广到其他表面配体,如牛血清白蛋白,杂乱的 MAC-1 也与该蛋白结合。这些结果表明,中性粒细胞能够根据其黏附环境表现出多种运动模式。