Faculty Collaboration Database

Improved treatment of systemic blood infections using antibiotics with extracorporeal opsonin hemoadsorption. Biomaterials 2015 Oct;67:382-92

Date

08/09/2015

Pubmed ID

26253638

DOI

10.1016/j.biomaterials.2015.07.046

Scopus ID

2-s2.0-84939621978 (requires institutional sign-in at Scopus site)   60 Citations

Abstract

Here we describe development of an extracorporeal hemoadsorption device for sepsis therapy that employs commercially available polysulfone or polyethersulfone hollow fiber filters similar to those used clinically for hemodialysis, covalently coated with a genetically engineered form of the human opsonin Mannose Binding Lectin linked to an Fc domain (FcMBL) that can cleanse a broad range of pathogens and endotoxin from flowing blood without having to first determine their identity. When tested with human whole blood in vitro, the FcMBL hemoadsorption filter (FcMBL-HF) produced efficient (90-99%) removal of Gram negative (Escherichia coli) and positive (Staphylococcus aureus) bacteria, fungi (Candida albicans) and lipopolysaccharide (LPS)-endotoxin. When tested in rats, extracorporeal therapy with the FcMBL-HF device reduced circulating pathogen and endotoxin levels by more than 99%, and prevented pathogen engraftment and inflammatory cell recruitment in the spleen, lung, liver and kidney when compared to controls. Studies in rats revealed that treatment with bacteriocidal antibiotics resulted in a major increase in the release of microbial fragments or 'pathogen-associated molecular patterns' (PAMPs) in vivo, and that these PAMPs were efficiently removed from blood within 2 h using the FcMBL-HF; in contrast, they remained at high levels in animals treated with antibiotics alone. Importantly, cleansing of PAMPs from the blood of antibiotic-treated animals with the FcMBL-hemoadsorbent device resulted in reduced organ pathogen and endotoxin loads, suppressed inflammatory responses, and resulted in more stable vital signs compared to treatment with antibiotics alone. As PAMPs trigger the cytokine cascades that lead to development of systemic inflammatory response syndrome and contribute to septic shock and death, co-administration of FcMBL-hemoadsorption with antibiotics could offer a more effective approach to sepsis therapy.

Author List

Didar TF, Cartwright MJ, Rottman M, Graveline AR, Gamini N, Watters AL, Leslie DC, Mammoto T, Rodas MJ, Kang JH, Waterhouse A, Seiler BT, Lombardo P, Qendro EI, Super M, Ingber DE

Author

Tadanori Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adsorption
Animals
Anti-Bacterial Agents
Bacterial Infections
CHO Cells
Cricetinae
Cricetulus
Extracorporeal Circulation
Hemofiltration
Humans
Lipopolysaccharides
Male
Opsonin Proteins
Rats, Wistar