Defensins impair phagocytic killing by neutrophils in biomaterial-related infection

The implantation of foreign material carries a risk of infection which freq uently is resistant to all treatment short of removing the implant. We have previously shown that these materials activate neutrophils by contact, lea ding to production of oxygen free radicals accompanied by release of granul e products. Such activation further results in depletion of local host defe nses, including the capacity of biomaterial-activated neutrophils to kill b acteria. Among the granule products released from neutrophils are small cat ionic antibacterial peptides (human neutrophil peptides [HNP]) known as def ensins. Here we tested the hypothesis that defensins, released from activat ed neutrophils onto the surface of biomaterials, might play a role in the d eactivation of subsequent neutrophil populations. Incubation of neutrophils with purified HNP resulted in a dose-related impairment of stimulus-induce d oxygen radical production and of phagocytic killing. Furthermore, fresh n eutrophils added to biomaterial-associated neutrophils exhibited impaired p hagocytic killing. This impairment could be abrogated by antibody to HNP bu t not by an irrelevant antibody Taken together, these observations support the idea that neutrophils activated at a material surface can create, by me ans of HNP release, an environment hostile to their microbicidal function a nd that of their infiltrating brethren.