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Department of Chemical Engineering, The Johns Hopkins University, Baltimore, Maryland 21218
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/sLex-bearing LS174T cells and the
CD54-expressing/sLex-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.
CD11a/CD18; CD11b/CD18; L-selectin; polymorphonuclear leukocytes; LS174T cells; HCT-8 cells
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