Alteration of leukocyte motility on plasma-conditioned prosthetic biomaterial, ePTFE, via a flow-responsive cell adhesion molecule, CD43.

The physiologic determinants of leukocyte migration on vascular prosthetic biomaterials remain poorly understood, despite their relevance to the control of periprosthetic infection. Using hemodynamic exposure of human polymorphonuclear leukocytes adherent to expanded polytetrafluoroethylene (ePTFE) in vitro, we investigated the role of fluid shear in regulating leukocyte migratory behavior on plasma-adsorbed, prosthetic vascular biomaterial. The presence of flow at a wall shear stress of 25 dyn/cm(2) increased the degree of leukocyte displacement along the flow direction without altering the degree of overall cell attachment. Moreover, plasma-ePTFE elicited a lower overall degree of displacement under flow in comparison with untreated ePTFE. We further probed the molecular level regulation of leukocyte migratory responses under flow through the immunocytochemical quantification of specific leukocyte adhesion molecules and determined that CD43, a cell adhesion molecule, was upregulated via flow exposure for leukocytes adherent to plasma-ePTFE, whereas basal levels of CD43 expression were not significantly altered on untreated ePTFE. When flow-exposed, adherent leukocytes were incubated in the presence of substrate immobilized anti-CD43 immunoglobulin, the degree of cell displacement along flow was found to be significantly enhanced on plasma-ePTFE. Quantification of the cell population redistribution under flow using a modified random motility model, indicated that the incorporation of anti-CD43 on plasma-ePTFE led to a significant increase (243 +/- 60%) in the cell dispersion coefficient, mu(D), whereas only a minimal increase (61 +/- 30%) was detected on non-adsorbed ePTFE. Overall, our results suggest that flow exposure can induce the migration of leukocytes adherent to prosthetic materials in a substrate-dependent manner. An important implication of our study is that, although biomaterials exposed to plasma intrinsically passivate leukocyte migration even under hemodynamic conditions, it may be possible to promote cell motility by targeting a specific, flow-responsive, adhesion molecule.