Silver Nanoparticles Attenuate the Antimicrobial Activity of the Innate Immune System by Inhibiting Neutrophil-Mediated Phagocytosis and Reactive Oxygen Species Production

Abstract

Moran Huang,1,* Kai Ye,1,* Tu Hu,2,* Kexin Liu,3 Mengzhen You,3 Lei Wang,1 Hui Qin1 1Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Musculoskeletal Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 3Department of General Practice, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Qin; Lei WangDepartment of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, No. 600 Yishan Road, Shanghai, People’s Republic of ChinaTel [phone]; [phone]Fax [phone]Email [email protected]; [email protected]: Despite the extensive development of antibacterial biomaterials, there are few reports on the effects of materials on the antibacterial ability of the immune system, and in particular of neutrophils. In this study, we observe differences between the in vivo and in vitro anti-infective efficacies of silver nanoparticles (AgNPs). The present study was designed to further explore the mechanism for this inconsistency using ex vivo models and in vitro experiments.Methods: AgNPs were synthesized using the polyol process and characterized by transmission electron microscopy and X-ray photoelectron spectroscopy. The antibacterial ability of AgNPs and neutrophils was tested by the spread-plate method. The infected air pouch model was prepared to detect the antimicrobial ability of AgNPs in vivo. Furthermore, blood-AgNPs-bacteria co-culture model and reactive oxygen species (ROS) measurement were used to evaluate the effect of AgNPs to neutrophil-mediated phagocytosis and ROS production.Results: The antibacterial experiments in vitro showed that AgNPs had superior antibacterial properties in cell compatible concentration. While, AgNPs had no significant antibacterial effect in vivo, and pathological section in AgNPs group indicated less neutrophil infiltration in inflammatory site than S. aureus group. Furthermore, AgNPs were found to reduce the phagocytosis of neutrophils and inhibit their ability to produce ROS and superoxide during ex vivo and in vitro experiments.Conclusion: This study selects AgNPs as the representative of inorganic nano-biomaterials and reveals the phenomenon and the mechanism underlying the significant AgNPs-induced inhibition of the antibacterial ability of neutrophils, and may have a certain enlightening effect on the development of biomaterials in the future. In the fabrication of antibacterial biomaterials, however, attention should be paid to both cell and immune system safety to make the antibacterial properties of the biomaterials and innate immune system complement each other and jointly promote the host’s ability to resist the invasion of pathogenic microorganisms.Keywords: antibacterial biomaterials, polymorphonuclear neutrophils, silver nanoparticles, immune system

Keywords

• antibacterial biomaterials
• polymorphonuclear neutrophils
• silver nanoparticles
• immune system