Edwards Erin Elizabeth, Oh Jaeho, Anilkumar Ananyaveena, Birmingham Katherine Gayle, Thomas Susan Napier
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA.
Oncotarget. 2017 Jun 28;8(48):83585-83601. doi: 10.18632/oncotarget.18786. eCollection 2017 Oct 13.
The ability of leukocytic cells to engage selectins via rolling adhesion is critical to inflammation, but selectins are also implicated in mediating metastatic dissemination. Using a microfluidic- and flow-based cell adhesion chromatography experimental and analytical technique, we interrogated the cell-subtype differences in engagement and sustainment of rolling adhesion on P-, E-, and L-selectin-functionalized surfaces in physiological flow. Our results indicate that, particularly at low concentrations of P-selectin, metastatic but not leukocytic cells exhibit reduced rolling adhesion persistence, whereas both cell subtypes exhibited reduced persistence on L-selectin and high persistence on E-selectin, differences not revealed by flow cytometry analysis or reflected in the extent or velocity of rolling adhesion. Conditions under which adhesion persistence was found to be significantly reduced corresponded to those exhibiting the greatest sensitivity to a selectin-antagonist. Our results suggest that potentially therapeutically exploitable differences in metastatic and leukocytic cell subtype interactions with selectins in physiological flow are identifiable through implementation of functional assays of adhesion persistence in hemodynamic flow utilizing this integrated, flow-based cell adhesion chromatography analytical technique.
白细胞通过滚动黏附与选择素结合的能力对炎症至关重要，但选择素也参与介导转移扩散。我们使用基于微流控和流动的细胞黏附色谱实验及分析技术，研究了在生理流动条件下，转移性细胞和白细胞在P-、E-和L-选择素功能化表面上进行滚动黏附的结合和维持过程中的细胞亚型差异。我们的结果表明，特别是在低浓度的P-选择素情况下，转移性细胞而非白细胞表现出滚动黏附持久性降低，而两种细胞亚型在L-选择素上均表现出持久性降低，在E-选择素上则表现出高持久性，这些差异通过流式细胞术分析未揭示，也未反映在滚动黏附的程度或速度上。发现黏附持久性显著降低的条件与对选择素拮抗剂敏感性最高的条件相对应。我们的结果表明，通过利用这种基于流动的综合细胞黏附色谱分析技术，在血液动力学流动中实施黏附持久性功能测定，可识别转移性细胞和白细胞亚型在生理流动中与选择素相互作用的潜在治疗可利用差异。
