NEUTROPHIL ACTIVATION BY EXPANDED POLYTETRAFLUOROETHYLENE IS DEPENDENT ON THE INDUCTION OF PROTEIN-PHOSPHORYLATION

Background. Polymorphonuclear leukocyte (PMN) activation after inter-a ction with implantable surfaces has been previously reported. The purp ose of this study was to examine the mechanism of PMN activation in re sponse to expanded polytetrafluoroethylene (ePTFE). Methods. To demons trate PMN activation, the cumulative production of superoxide was meas ured on uncoated, plasma coated, or albumin coated ePTFE discs. Chroma tin 51-labeled PMNs were used to measure binding. Cell structure was e xamined by scanning electron microscopy. Results. By 4 hours PMN activ ation on either uncoated or plasma coated ePTFE was approximately 30% of phorbol 12-myristate 13-acetate-induced activation. Albumin inhibit ed PMN activation by ePTFE. No apparent correlation existed between ch romium 51-labeled PMN binding and cell activation on the surfaces. Pre treatment of the cells with the protein kinase inhibitors bisindolylal eimide or genistein resulted in marked inhibition of superoxide produc tion on the uncoated and plasma coated ePTFE surfaces, whereas binding to these surfaces was not affected. PMNs spread on the uncoated surfa ce and transmigrated into the plasma coated ePTFE surface. These effec ts of ePTFE on cell structure were inhibited by bisindolylmaleimide an d genistein. Conclusions. ePTFE induced PMN activation, as measured by superoxide production, and changes in cell behavior are dependent on the activation of signaling pathways that involve protein phosphorylat ion events.