Indirect Bactericidal Properties of Recombinant Human Bone Morphogenetic Protein 2 In Vitro

Abstract

Bone morphogenetic proteins (BMPs) are secreted cytokines and are involved in various metabolic functions and inflammatory processes in different organs. The purpose of this study was to investigate whether BMPs also possess antimicrobial properties in direct or indirect ways. Antibacterial properties of recombinant human BMP2 (rhBMP2) were tested on 4 bacteria species (Staphylococcus aureus, Escherichia coli, Streptococcus mitis, Streptococcus constellatus) to examine the potential synergism of rhBMP2 with antibiotics. Indirect antibacterial properties were tested by infecting neutrophils with rhBMP2 and bacteria to investigate bacterial survival. Reactive oxidative species (ROS) production in neutrophils in the presence of rhBMP2 also was tested. RhBMP2 in cardboard disks or sponge collagen as carriers did not show antibacterial activity against all tested bacteria. Further, synergism of rhBMP2 with antibiotics was not evident. Survival of bacteria inoculated with neutrophils and rhBMP2 led to a marked decrease in bacterial survival compared with neutrophils without rhBMP2. Although rhBMP2 inoculation of neutrophils alone did not induce ROS, its presence with the bacterial infection showed augmented ROS production for all tested bacteria. RhBMP2 did not show direct antibacterial properties but did exhibit an indirect bactericidal effect in the presence of neutrophils. ROS production indicated that rhBMP2 has a role as a priming agent for neutrophils by augmenting their bactericidal capabilities and suggests the importance of its presence in contaminated surgical bone augmentation sites.