Effect of plasma and matrix proteins on defensin-induced impairment of phagocytic killing by adherent neutrophils.

Abstract

Infection is too often associated with prosthetic devices. Increased susceptibility to infection at these surgical sites appears to be associated with defective local phagocytic killing. The mechanisms for neutrophil down-regulation, however, continue to be obscure. We have recently demonstrated that cytotoxic substances are released from granulocytes associated with materials. One group of releasants, the cationic human neutrophil peptide(s) (also called defensins) not only impairs the antimicrobial capacity of the granulocyte that releases it but also impairs bystander phagocytes. Because plasma or matrix proteins soon become associated with implants, we investigated the interactive effect of adding these proteins, singly and in combination, on the microbicidal effect of bystander cells. Some plasma/matrix proteins (whole plasma, albumin, fibrinogen, and fibronectin) strongly interfered with the anti-microbicidal effects generated by neutrophil-polystyrene interaction. Other proteins (vitronectin and laminin) were without effect. These results suggest that protein composition at the prosthetic implant site could have a significant effect on infectivity, depending on whether neutrophils releasants were attenuated. In the absence of attenuation, the local environment would be hostile to host defenses, permitting bacterial survival and proliferation.