Endotoxin-neutralizing activity of hen egg phosvitin.
Endotoxin, also known as lipopolysaccharide (LPS), is responsible for initiating host responses leading to inflammation and sometimes unwanted sepsis, which is associated with high mortality in patients. No therapeutic agents to date are efficacious enough to protect patients from LPS-mediated tissue damage and organ failure. Previously, egg yolk protein phosvitin (Pv) in zebrafish has been shown to act as a pattern recognition receptor, capable of binding to the microbial cell wall components including LPS, we therefore wonder if it has the capacity to block LPS toxicity. In this study we first demonstrated that hen Pv, a naturally occurring protein rich in egg yolk, had antimicrobial activity against Escherichia coli and Staphylococcus aureus under thermal stress, and then showed that Pv was able to bind to LPS, lipoteichoic acid and peptidoglycan as well as the microbes E. coli and S. aureus. More importantly, we revealed that Pv significantly inhibited LPS-induced tumor-necrosis factor (TNF)-α release from murine RAW264.7 cells and considerably reduced serum TNF-α level in mice. Additionally, hen Pv could promote the survival rate of the endotoxemia mice. Furthermore, hen Pv displayed no cytotoxicity to murine RAW264.7 macrophages and no hemolytic activity towards human red blood cells. Taken together, these data suggest that Pv is an endotoxin-neutralizing agent with a therapeutic potential in clinical treatment of LPS-induced sepsis.
Laboratory for Evolution and Development, Institute of Evolution & Marine Biodiversity and Department of Marine Biology, Ocean University of China, Qingdao 266003, China.
Jie
J
Ma
Hongmiao
H
Wang
Yongjun
Y
Wang
Shicui
S
Zhang
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D010774:Phosvitin / Q000494:pharmacology*; D018805:Sepsis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D010774:Phosvitin