title: Two-dimensional kinetics of beta 2-integrin and ICAM-1 bindings between neutrophils and melanoma cells in a shear flow.
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 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.
authors.affiliation: Dept. of Bioengineering, The Pennsylvania State University, University Park, PA 16802-6804, USA.
authors.forename: Shile
authors.initials: S
authors.lastname: Liang
authors.forename: Changliang
authors.initials: C
authors.lastname: Fu
authors.forename: Desiree
authors.initials: D
authors.lastname: Wagner
authors.forename: Huiguang
authors.initials: H
authors.lastname: Guo
authors.forename: Dongying
authors.initials: D
authors.lastname: Zhan
authors.forename: Cheng
authors.initials: C
authors.lastname: Dong
authors.forename: Mian
authors.initials: M
authors.lastname: Long
mesh_terms: D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D002449:Cell Aggregation; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D018056:Hemorheology / Q000379:methods; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007700:Kinetics; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D008954:Models, Biological; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D011485:Protein Binding; D013314:Stress, Mechanical
chemical_list: D018821:CD18 Antigens; D018799:Intercellular Adhesion Molecule-1; D009240:N-Formylmethionine Leucyl-Phenylalanine