Neutrophil survival on biomaterials is determined by surface topography.
OBJECTIVE
Cardiovascular device-centered infections are a major cause of hospital morbidity, mortality, and expense. Caused by opportunistic bacteria, this phenomenon is thought to arise because of a defect in neutrophil bacterial killing. We have shown that neutrophils that adhere to polystyrene remain viable, whereas neutrophils that adhere to the vascular biomaterials expanded polytetrafluoroethylene (ePTFE) and Dacron undergo a rapid nonapoptotic death. This study was designed to test the hypothesis that surface topography is a determinant of the nonapoptotic death response of neutrophils to biomaterials.


METHODS
We took advantage of the ease with which a polystyrene surface can be manipulated to examine the effect of surface topography on neutrophil viability. Neutrophils were exposed to smooth or roughened polystyrene surfaces both in vivo and in vitro. Changes in cell membrane permeability and production of reactive oxygen species by individual cells were monitored with fluorescent dyes.


RESULTS
Host cells and isolated human neutrophils died rapidly after adhesion to roughened polystyrene. Neutrophils adherent to roughened surfaces produced more reactive oxygen intermediates than those adherent to smooth surfaces and were first to die. The cell death response precipitated by expanded polytetrafluoroethylene, Dacron, or the roughened surfaces was significantly reduced with treatment of the neutrophils with catalase, diphenylene iodonium, or the src kinase inhibitor PP2 before adhesion.


CONCLUSIONS
Neutrophil adhesion to roughened materials triggers rapid production of reactive oxygen species and precipitates a nonapoptotic cell death. Understanding the material properties that trigger these responses is essential to development of the next generation of implantable biomaterials.
Chang
Susan
S
Department of Surgery, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ, USA.
Popowich
Yale
Y
Greco
Ralph S
RS
Haimovich
Beatrice
B
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*; D011093:Polyethylene Terephthalates / Q000494:pharmacology; D011137:Polystyrenes / Q000494:pharmacology; D011138:Polytetrafluoroethylene / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012016:Reference Values; D013499:Surface Properties; D013997:Time Factors; D019371:Topography, Medical
D001672:Biocompatible Materials; D011093:Polyethylene Terephthalates; D011137:Polystyrenes; D017382:Reactive Oxygen Species; D011138:Polytetrafluoroethylene; D006861:Hydrogen Peroxide