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Two-dimensional kinetics of [[beta].sub.2]-integrin and ICAM-1 bindings between neutrophils and melanoma cells in a shear flow

Authors :
Liang, Shile
Fu, Changliang
Wagner, Desiree
Guo, Huiguang
Zhan, Dongying
Dong, Cheng
Long, Mian
Source :
The American Journal of Physiology. March, 2008, Vol. 294 Issue 3, pC743, 11 p.
Publication Year :
2008

Abstract

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].sub.2]-integrin (lymphocyte function-associated antigen-1 and/or Mac-l) on polymorphonuclear neutrophils (PMNs) and 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 a near-wall region of the vascular endothelium, therefore enhancing subsequent extravasation of melanoma cells in the microcirculations. Kinetics of integrin-ligand bindings in a shear flow is the determinant of such a process, which has not been well understood. In the present study, interactions of PMNs with WM9 melanoma cells were investigated to quantify the kinetics of [[beta].sub.2]-integrin and 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 first increased before 60 s and then decreased with shear durations. Melanoma-PMN aggregation was also found to be 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].sub.2]-integrin and ICAM-1 bindings were obtained by individual or global fittings, which were comparable to respectively published values. These findings provide new quantitative understanding of the biophysical basis of leukocyte-tumor cell interactions mediated by specific receptor-ligand interactions under shear flow conditions. heterotypic cell aggregation; adhesion molecule; leukocyte; tumor cell; reverse rate; binding affinity; probabilistic model; polymorpho-nuclear neutrophils; intercellular adhesion molecule-1

Details

Language :
English
ISSN :
00029513
Volume :
294
Issue :
3
Database :
Gale General OneFile
Journal :
The American Journal of Physiology
Publication Type :
Academic Journal
Accession number :
edsgcl.177265870