Kukreti S, Konstantopoulos K, Smith C W, McIntire L V
Cox Laboratory for Biomedical Engineering, Rice University, Houston, TX 77251-1892, USA.
Blood. 1997 Jun 1;89(11):4104-11.
This study identifies multiple pathways used by monocytes to adhere to 4-hour interleukin-1beta stimulated human umbilical vein endothelial cells under flow conditions. Physiologic shear stresses were simulated in a flow chamber with parallel plate geometry; quantitation of primary adhesion, secondary adhesion, and transmigration was performed using phase contrast videomicroscopy. Neuraminidase treatment of monocytes reduced primary interaction by 50%, whereas blocking L-selectin or very late antigen-4 showed significant but smaller effects (approximately 30% inhibition). However, a combined treatment against all three pathways was able to reduce interaction by 80%. Blocking beta2 and alpha4 integrin pathways together inhibited secondary/firm adhesion by 75%. Only 40% of firmly adherent monocytes transmigrated across the endothelial monolayer with significantly increased transmigration times when both beta2 and alpha4 integrins were blocked. These results demonstrate that monocytes can use multiple receptors to interact with endothelial cells at both primary and secondary adhesion stages, and that these pathways have to be blocked simultaneously for maximum inhibition.
本研究确定了在流动条件下，单核细胞用于黏附于经4小时白细胞介素-1β刺激的人脐静脉内皮细胞的多种途径。在具有平行板几何形状的流动腔中模拟生理剪切应力；使用相差视频显微镜对初始黏附、二次黏附和迁移进行定量分析。用神经氨酸酶处理单核细胞可使初始相互作用降低50%，而阻断L-选择素或极晚期抗原-4则显示出显著但较小的作用（约30%的抑制率）。然而，针对所有这三种途径的联合处理能够使相互作用降低80%。同时阻断β2和α4整合素途径可抑制二次/牢固黏附达75%。当β2和α4整合素均被阻断时，只有40%牢固黏附的单核细胞能够穿过内皮单层迁移，且迁移时间显著增加。这些结果表明，单核细胞在初始黏附和二次黏附阶段均可利用多种受体与内皮细胞相互作用，并且必须同时阻断这些途径才能实现最大程度的抑制。
