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.

中文翻译：

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P-选择素和ICAM-1协同作用介导THP-1单核细胞在血流动力学中的粘附与长度有关。

单核细胞的紧密协调募集，其后代对各种生理学和病理生理学过程的发展和解决至关重要，与时间进程，严重性和病理学解决有关。使用基于时空分析和粘附蛋白微模式的基于微流的细胞粘附测定，我们研究了粘附分子呈递长度对THP-1单核细胞滚动与由P-介导的牢固粘附的影响，该长度随疾病和阶段而在体内变化选择素和/或ICAM-1的血流动力学。我们的结果表明，P-选择素和ICAM-1的共同呈递可大大减少维持流动中粘附所需的粘合剂基质的长度，并且P-选择素与ICAM-1协同发挥作用，从而大大增强THP-1的牢固粘附力。还发现这种协同作用还与细胞滚动速度降低和长度增加的次级细胞捕获相关。我们的结果表明，在指导单核细胞运输效率方面，发炎的微血管微环境的局部重塑的病理生理学后果。