Edwards Erin Elizabeth, Thomas Susan Napier
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
Integr Biol (Camb). 2017 Apr 18;9(4):313-327. doi: 10.1039/c7ib00020k.
The tightly orchestrated recruitment of monocytes, whose progeny are critical to the progression and resolution of various physiological and pathophysiological processes, is implicated in the time course, severity, and resolution of pathology. Using a microfluidic-based cell adhesion assay integrating spatiotemporal analyses and micropatterning of adhesive proteins, we interrogated the effects of adhesive molecule presentation length, which varies in vivo with disease and stage, on THP-1 monocyte cell rolling versus firm adhesion mediated by P-selectin and/or ICAM-1 in hemodynamic flow. Our results indicate that co-presentation of P-selectin and ICAM-1 substantially decreases the length of adhesive substrate required to sustain adhesion in flow and that P-selectin functions synergistically with ICAM-1 to substantially enhance THP-1 firm adhesion. This synergy was found to furthermore correlate with diminished cell rolling velocities and length-enhanced secondary cell capture. Our results suggest pathophysiological ramifications for local remodeling of the inflamed microvascular microenvironment in directing the efficiency of monocyte trafficking.
单核细胞的募集过程受到严格调控，其后代对于各种生理和病理生理过程的进展及消退至关重要，这一过程与病理的时间进程、严重程度及消退有关。我们利用基于微流控的细胞黏附试验，该试验整合了时空分析和黏附蛋白的微图案化技术，研究了黏附分子呈现长度对THP-1单核细胞在血流动力学流动中由P-选择素和/或细胞间黏附分子-1（ICAM-1）介导的滚动与牢固黏附的影响，黏附分子呈现长度在体内会因疾病和阶段而有所不同。我们的结果表明，P-选择素和ICAM-1的共同呈现显著降低了在流动中维持黏附所需的黏附底物长度，并且P-选择素与ICAM-1协同发挥作用，显著增强了THP-1的牢固黏附。此外，发现这种协同作用与细胞滚动速度的降低以及二次细胞捕获长度的增加相关。我们的结果提示了炎症微血管微环境的局部重塑在指导单核细胞运输效率方面的病理生理影响。
