Force-dependent bond dissociation govern rolling of HL-60 cells through E-selectin.
E-selectin-mediated rolling on vascular surface of circulating leukocyte on vascular surface is a key initial event during inflammatory response and lymphocyte homing. This event depends not only on the specific interactions of adhesive molecules but also on the hemodynamics of blood flow. Little is still understood about whether wall shear stress or shear rate regulates the rolling. With flow chamber techniques, we here measured the effects of transport, shear stress and cell deformation on rolling of both unfixed and fixed HL-60 cells on E-selectin either in the absence or in the presence of 3% Ficoll in medium at various wall shear stresses from 0.05 to 0.7 dyn/cm(2). The results demonstrated a triphasic force-dependent rolling, that is, as increasing of force, the rolling would be accelerated firstly, then followed a decelerating phase occurred at the initial shear threshold of about 0.1 dyn/cm(2), and lastly returned to an accelerating process starting at the optimal shear threshold of 0.35 dyn/cm(2) approximately. The catch bond regime was completely reflected to rolling behaviors, such as tether lifetime, cell stop time and rolling velocity, meaning that the dominant factor to govern rolling is force. The initial shear threshold might be the minimum level of wall shear stress to sustain a stationary rolling, and the optimal shear threshold would make rolling to the most stable and regular. These findings strongly elucidate the catch bond mechanism for flow-enhanced rolling through E-selectin since longer bond lifetimes led to slower and stabler rolling.
School of Life Science, Sun Yat-Sen University, Guangzhou 510275, China.
Quhuan
Q
Li
Ying
Y
Fang
Xiaoru
X
Ding
Jianhua
J
Wu
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D019040:E-Selectin / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D008024:Ligands
D000911:Antibodies, Monoclonal; D019040:E-Selectin; D008024:Ligands; D004492:Edetic Acid