Two-Dimensional Kinetics Of Beta(2)-Integrin And Icam-1 Bindings Between Neutrophils And Melanoma Cells In A Shear Flow
Data(s) |
2008
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Resumo |
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 ( lymphocyte function-associated antigen-1 and/or Mac-1) 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(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(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. |
Identificador | |
Idioma(s) |
英语 |
Fonte |
American Journal Of Physiology-Cell Physiology, 2008, 294(3): C743-C753 |
Palavras-Chave | #Heterotypic Cell Aggregation #Adhesion Molecule #Leukocyte #Tumor Cell #Reverse Rate #Binding Affinity #Probabilistic Model #Polymorpho-Nuclear Neutrophils #Intercellular Adhesion Molecule-1 #Intercellular-Adhesion Molecule-1 #Ligand-Mediated Adhesion #Hydrodynamic Shear #L-Selectin #Malignant-Melanoma #Dynamic Regulation #Variant Isoforms #Stable Adhesion #Latex Spheres #P-Selectin |
Tipo |
期刊论文 |