Biomaterial-neutrophil interactions: dysregulation of oxidative functions of fresh neutrophils induced by prior neutrophil-biomaterial interaction.

Biomaterial-associated infection results in increased morbidity and mortality, and may occur because of nonproductive premature activation of neutrophils resulting in impaired phagocyte function at the biomaterial surface in the event of bacterial challenge. To further explore the effects of this premature activation, we evaluated the supernatants of biomaterial associated neutrophils to determine whether soluble mediators were released, and the likely role of these mediators. We show that these supernatants contain a chemoattractant and thereby induce chemotaxis by fresh neutrophils. No evidence of enhanced oxidative free radical production by either unstimulated neutrophils or a primed response to other mediators occurs when neutrophils were incubated with these supernatants. We also examined the effect of adding fresh neutrophils to a biomaterial surface containing a previous inoculum of neutrophils, and observed that the fresh cells did not become stimulated to release reactive oxygen intermediates (ROI) and also exhibited impaired killing of staphylococci. These studies suggest that not only does the biomaterial surface activate the initial wave of neutrophils but that subsequent waves of neutrophils exhibit an impaired host-defense function. These results are consistent with the known impairment of host defense in the presence of biomaterials, and provide evidence for a long-term down-regulation of neutrophil function at biomaterial surfaces.