Spreading of human neutrophils on an ICAM-1-immobilized substrate under shear flow  

作　　者：ZHAN DongYing ZHANG Yan LONG Mian 

机构地区：[1]Key Laboratory of Microgravity,National Microgravity Laboratory and Center of Biomechanics and Bioengineering,Institute of Mechanics,Chinese Academy of Sciences,Beijing 100190,China

出　　处：《Chinese Science Bulletin》2012年第7期769-775,共7页

基　　金：supported by the National Natural Science Foundation of China (30730032 and 10902117);Chinese Academy of Sciences Knowledge Innovation Project (KJCX2-YW-L08 and Y2010030);the National Basic Research Program of China (2011CB710904)

摘　　要：Neutrophil (PMN) spreading on endothelium, mediated by the interactions between surface-bound β2 integrin and intercellular adhesion molecule-1 (ICAM-1) in the inflammatory cascade, is crucial for PMN post-adhesion and trans-migration in blood flow. The underlying mechanisms by which shear flow regulates PMN spreading dynamics are not well understood. Here, a parallel-plate flow chamber assay was applied to quantify the time course of PMN adhesion and spreading on an ICAM-1-immobilized substrate. Two types of shear flow, steady flows at shear stresses of 0.2, 0.5, and 1 dyne/cm2 and stepwise flows at 0, 1, and 10 dyne/cm2, were used to elucidate the impact of shear flow on cell adhesion and spreading. The number of adhered PMNs, the fraction of spreading PMNs and the projected area of spread PMNs were determined and were found to correlate with the distribution of surface-bound β2 integrin subunit (CD11a, CD11b, or CD18). The results indicate that PMN spreading on an ICAM-1 substrate is bi-directionally regulated under shear flow. CD11a, CD11b and CD18 subunits of β2 integrin contribute distinctly to PMN spreading on ICAM-1 substrates. This work provides new insights into understanding PMN spreading on the endothelium, mediated by β2 integrin and ICAM-1 under shear flow.Neutrophil （PMN） spreading on endothelium, mediated by the interactions between surface-bound β2 integrin and intercellular adhesion molecule-1 （ICAM-1） in the inflammatory cascade, is crucial for PMN post-adhesion and trans-migration in blood flow. The underlying mechanisms by which shear flow regulates PMN spreading dynamics are not well understood. Here, a paral- lel-plate flow chamber assay was applied to quantify the time course of PMN adhesion and spreading on an ICAM-l-immobilized substrate. Two types of shear flow, steady flows at shear stresses of 0.2, 0.5, and 1 dyne/cm2 and stepwise flows at 0, 1, and 10 dyne/cm2, were used to elucidate the impact of shear flow on cell adhesion and spreading. The number of adhered PMNs, the fraction of spreading PMNs and the projected area of spread PMNs were determined and were found to correlate with the distri- bution of surface-bound β2 integrin subunit （CD1 l a, CD1 lb, or CD18）. The results indicate that PMN spreading on an ICAM-I substrate is bi-directionally regulated under shear flow. CD1 la, CD1 lb and CD18 subunits of β2 integrin contribute distinctly to PMN spreading on ICAM-1 substrates. This work provides new insights into understanding PMN spreading on the endothelium, mediated by β2 integrin and ICAM-1 under shear flow.

关 键 词：ICAM-1 中性粒细胞 剪切流场 基板 传播 细胞间粘附分子1 扩散动力学 血管内皮细胞 

分 类 号：Q25[生物学—细胞生物学] Q26