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.