Neutrophil activation by expanded polytetrafluoroethylene is dependent on the induction of protein phosphorylation.
BACKGROUND
Polymorphonuclear leukocyte (PMN) activation after interaction with implantable surfaces has been previously reported. The purpose of this study was to examine the mechanism of PMN activation in response to expanded polytetrafluoroethylene (ePTFE).


METHODS
To demonstrate PMN activation, the cumulative production of superoxide was measured on uncoated, plasma coated, or albumin coated ePTFE discs. Chromium 51-labeled PMNs were used to measure binding. Cell structure was examined by scanning electron microscopy.


RESULTS
By 4 hours, PMN activation on either uncoated or plasma coated ePTFE was approximately 30% of phorbol 12-myristate 13-acetate-induced activation. Albumin inhibited PMN activation by ePTFE. No apparent correlation existed between chromium 51-labeled PMN binding and cell activation on the surfaces. Pretreatment of the cells with the protein kinase inhibitors bisindolylmaleimide or genistein resulted in marked inhibition of superoxide production on the uncoated and plasma coated ePTFE surfaces, whereas binding to these surfaces was not affected. PMNs spread on the uncoated surface and transmigrated into the plasma coated ePTFE surface. These effects of ePTFE on cell structure were inhibited by bisindolylmaleimide and 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 phosphorylation events.
Katz
D A
DA
Department of Surgery, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903.
Haimovich
B
B
Greco
R S
RS
D002448:Cell Adhesion; D019833:Genistein; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D016023:Integrins / Q000502:physiology; D007529:Isoflavones / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010766:Phosphorylation; D011138:Polytetrafluoroethylene / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D011506:Proteins / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D007211:Indoles; D016023:Integrins; D007529:Isoflavones; D008301:Maleimides; D011506:Proteins; D013481:Superoxides; D011138:Polytetrafluoroethylene; D019833:Genistein; D011493:Protein Kinase C