title: Fluid shear- and time-dependent modulation of molecular interactions between PMNs and colon carcinomas.
abstract: This study compares the effects of fluid shear on the kinetics, adhesion efficiency, stability, and molecular requirements of polymorphonuclear leukocyte (PMN) binding to two colon adenocarcinoma cell-lines, the CD54-negative/sLe(x)-bearing LS174T cells and the CD54-expressing/sLe(x)-low HCT-8 cells. The efficiency of PMN-colon carcinoma heteroaggregation decreases with increasing shear, with PMNs binding HCT-8 more efficiently than LS174T cells at low shear (50-200 s(-1)). In the low shear regime, CD11b is sufficient to mediate PMN binding to LS174T cells. In contrast, both CD11a and CD11b contribute to PMN-HCT-8 heteroaggregation, with CD54 on HCT-8 cells acting as a CD11a ligand at early time points. At high shear, only PMN-LS174T heteroaggregation occurs, which is initiated by PMN L-selectin binding to a sialylated, O-linked, protease-sensitive ligand on LS174T cells. PMN-LS174T heteroaggregation is primarily dependent on the intercellular contact duration (or shear rate), whereas PMN-HCT-8 binding is a function of both the intercellular contact duration and the applied force (or shear stress). Cumulatively, these studies suggest that fluid shear modulates the kinetics and molecular mechanisms of PMN-colon carcinoma cell aggregation.
authors.affiliation: Department of Chemical Engineering, The Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA.
authors.forename: Sameer
authors.initials: S
authors.lastname: Jadhav
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Konstantopoulos
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000503:physiopathology*; D002448:Cell Adhesion / Q000276:immunology; D002449:Cell Aggregation / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology / Q000503:physiopathology*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D009844:Oligosaccharides / Q000378:metabolism; D012212:Rheology; D000080506:Sialyl Lewis X Antigen; D013314:Stress, Mechanical; D014407:Tumor Cells, Cultured; D014783:Viscosity
chemical_list: D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine