Leukocyte-polytetrafluoroethylene interaction enhances proliferation of vascular smooth muscle cells via tumor necrosis factor-α secretion

Abstract

Intimal hyperplasia of vascular smooth muscle cells (VSMC) at the venous anastomosis of arteriovenous grafts represents the most common cause of vascular access failure in hemodialysis patients. Upstream release of growth factors from leukocytes activated by adhesion to the graft material may play a role in this lesion. We evaluated the effect of interaction of peripheral blood mononuclear cells (PBMC) with polytetrafluoroethylene (PTFE) on proliferation of VSMC. Vascular smooth muscle cell proliferation was significantly increased by conditioned media from human PBMC incubated with PTFE. Peripheral blood mononuclear cell adhesion to PTFE could not be antagonized by the β1 integrin ligand-containing peptide GRGDSP, but was attenuated by EDTA consistent with β2 integrin-mediated adhesion. Soluble scavenger receptor ligands at high concentrations had no effect on adhesion to FIFE excluding any contributory role of scavenger receptors in this interaction. Neutralizing antibodies to TNF-α significantly attenuated the mitogenic effect of PBMC/FIFE conditioned media and a marked increase in TNF- α secretion by PBMC on FIFE was detected by ELISA. These studies demonstrate that PBMC interaction with PTFE can promote proliferation of VSMC via increased production of TNF-α and perhaps other cytokines. Leukocyte interaction with FIFE causing enhanced secretion of TNF-α and consequent VSMC proliferation may account for the development of venous intimal hyperplasia in hemodialysis patients with arteriovenous grafts.