Hydrodynamic shear regulates the kinetics and receptor specificity of polymorphonuclear leukocyte- XXXX cell adhesive interactions.

@entity1 @entity5038 @entity5 @entity189 @entity1196 @entity1453 @entity9536 @entity694
The ability of @entity5 cells to metastasize hematogenously is regulated by their interactions with polymorphonuclear leukocytes (PMNs). However, the mechanisms mediating PMN binding to @entity5 cells under physiological shear forces remain largely unknown. This study was designed to characterize the molecular interactions between PMNs and @entity5 cells as a function of the dynamic shear environment, using two @entity1 @entity694 cell lines (LS174T and HCT-8) as models. PMN and @entity694 cell suspensions, labeled with distinct fluorophores, were sheared in a cone-and-plate rheometer in the presence of the PMN activator @entity5038 . The size distribution and cellular composition of formed aggregates were determined by flow cytometry. PMN binding to LS174T cells was maximal at 100 s(-1) and decreased with increasing shear. At low shear (100 s(-1)) PMN @entity9536 alone mediates PMN-LS174T heteroaggregation. However, @entity1196 , @entity1453 , and @entity9536 are all required for PMN binding to sialyl Lewis(x)-bearing LS174T cells at high shear (800 s(-1)). In contrast, sialyl Lewis(x)-low HCT-8 cells fail to aggregate with PMNs at high shear conditions, despite extensive adhesive interactions at low shear. Taken together, our data suggest that PMN @entity1196 initiates LS174T cell tethering at high shear by binding to sialylated moieties on the @entity189 cell surface, whereas the subsequent involvement of @entity1453 and @entity9536 converts these transient tethers into stable adhesion. This study demonstrates that the shear environment of the vasculature modulates the dynamics and molecular constituents mediating PMN- @entity5 cell adhesion.
