Am J Physiol Cell Physiol AJP: Gastrointestinal and Liver Physiology
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Am J Physiol Cell Physiol (January 16, 2008). doi:10.1152/ajpcell.00250.2007
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Submitted on June 12, 2007
Accepted on January 13, 2008

Two-dimensional (2D) kinetics of {beta}2 integrin-ICAM-1 bindings between neutrophils and melanoma cells

Shile Liang1, Changliang Fu2, Desiree Wagner1, Huiguang Guo3, Dongying Zhan2, Cheng Dong1*, and Mian Long3

1 Bioengineering, The Pennsylvania State University, University Park, Pennsylvania, United States
2 National Microgravity Laboratory and Center for Biomechanics and Bioengineering, Institue of Mechanics, Chinese Academy of Sciences, Beijing, Beijing, China
3 Beijing, Beijing, China; National Microgravity Laboratory and Center for Biomechanics and Bioengineering, Institue of Mechanics, Chinese Academy of Sciences, Beijing, Beijing, China

* To whom correspondence should be addressed. E-mail: cxd23{at}psu.edu.

Cell adhesion, mediated by specific receptor-ligand interactions, plays an important role in biological processes such as tumor metastasis and inflammatory cascade. For example, interactions between {beta}2 integrin (LFA-1 and/or Mac-1) on neutrophils (PMNs) and intercellular adhesion molecule (ICAM-1) on melanoma cells initiate the bindings of melanoma cells to PMNs within the tumor microenvironment in blood flow, which in turn activate PMN-melanoma cell aggregation in the near vascular endothelium (EC) region, therefore enhancing subsequent extravasation of melanoma cells in the microcirculations. Kinetics of integrin-ligand bindings in a shear flow is the determinant to such a process, which has not been well understood. In this study, interactions of PMNs to WM9 melanoma cells were investigated to quantify the kinetics of {beta}2 integrin-ICAM-1 bindings using a cone-plate viscometer that generates a linear shear flow combined with a two-color flow cytometry technique. Aggregation fractions exhibited a transition phase where it firstly increased and then decreased with shear durations generated by the cone-plate viscometer. It was also inversely correlated with the shear rate. A previously-developed probabilistic model was modified to predict the time dependence of aggregation fractions at different shear rates and medium viscosities. Kinetic parameters of {beta}2 integrin-ICAM-1 bindings were obtained by individual or global fittings, which were comparable to respectively published values. These findings provide a new insight into quantitative understandings to the biophysical bases of leukocyte-tumor cell interactions mediated by specific receptor-ligand interactions under shear flow conditions.




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S. Liang and C. Dong
Integrin VLA-4 enhances sialyl-Lewisx/a-negative melanoma adhesion to and extravasation through the endothelium under low flow conditions
Am J Physiol Cell Physiol, September 1, 2008; 295(3): C701 - C707.
[Abstract] [Full Text] [PDF]




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