PEGylated lysozymes with anti-septic effects in human endothelial cells and in mice

Biochemical and Biophysical Research Communications
W LeeJ Bae

Abstract

High mobility group box 1 (HMGB1) was recently shown to be an important extracellular mediator of severe vascular inflammatory disease, sepsis. Lysozyme (LYZ) has been shown to bind to bacterial lipopolysaccharide (LPS) and have a potential for playing a role in the therapy of inflammatory diseases. However, the effect of LYZ on HMGB1-induced septic response has not been investigated. Moreover, PEGylation effects on the antiseptic activity of LYZ are not known. Here, we show, for the first time, the anti-septic effects of PEGylated LYZ (PEG-LYZ) in HMGB1-mediated inflammatory responses in vitro and in vivo. Among four mono-PEGylated LYZs with different PEGylation sites (N-terminus, Lys(13), Lys(33), and Lys(97)), N-terminally PEGylated LYZ showed the highest activity. Subsequently, among three N-terminally PEGylated LYZs prepared with aldehyde-activated PEGs of 5, 10, and 20 kDa, 5 kDa-PEG-conjugated LYZ (P5-K(1)-LYZ) showed the highest antiseptic activity. The data showed that P5-K(1)-LYZ post-treatment effectively suppressed LPS-mediated release of HMGB1. P5-K(1)-LYZ also inhibited HMGB1-mediated hyperpermeability in human endothelial cells. Furthermore, P5-K(1)-LYZ reduced the cecal ligation and puncture (CLP)-induced releas...Continue Reading

References

Sep 21, 1973·European Journal of Biochemistry·G H GoodwinE W Johns
Aug 1, 1980·The Journal of Surgical Research·K A WichtermanI H Chaudry
Dec 1, 1993·British Journal of Pharmacology·R S BermanW Martin
Dec 6, 2001·American Journal of Respiratory and Critical Care Medicine·H WangK J Tracey
Dec 20, 2002·Nature·Jonathan Cohen
Mar 4, 2003·Nature Reviews. Drug Discovery·J Milton Harris, Robert B Chess
Sep 23, 2003·Advanced Drug Delivery Reviews·Paolo Caliceti, Francesco M Veronese
Dec 9, 2003·The Journal of Biological Chemistry·Jong Sung ParkEdward Abraham
Dec 30, 2003·Proceedings of the National Academy of Sciences of the United States of America·Huan YangKevin J Tracey
Aug 4, 2004·Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine·Andrew E SamaHaichao Wang
Mar 1, 2005·Journal of Leukocyte Biology·Huan YangKevin J Tracey
Apr 2, 2005·Nature Reviews. Immunology·Michael T Lotze, Kevin J Tracey
Oct 15, 2005·Nature Reviews. Drug Discovery·Jon A BurasMichail Sitkovsky
Oct 27, 2005·Journal of Agricultural and Food Chemistry·Jennifer Kovacs-NolanYoshinori Mine
Dec 7, 2007·Electrophoresis·Youyuan PengMyriam Taverna
Mar 11, 2009·Frontiers in Bioscience (Landmark Edition)·Madhav BhatiaShabbir Moochhala
Dec 17, 2009·Critical Care Medicine·Gareth L AcklandAlexander V Gourine
Dec 15, 2010·Microvascular Research·Rachel K WolfsonJoe G N Garcia
Nov 19, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Gianfranco Pasut, Francesco M Veronese
Oct 12, 2012·Archives of Pharmacal Research·Jong-Sup Bae
Nov 14, 2012·Journal of Chromatography. a·Benjamin MaiserJürgen Hubbuch
Jun 19, 2013·American Journal of Respiratory and Critical Care Medicine·James A Russell, Keith R Walley
Nov 28, 2013·Antimicrobial Agents and Chemotherapy·Alexander ZaborinJohn C Alverdy
May 13, 2014·Archives of Pharmacal Research·Sae-Kwang Ku, Jong-Sup Bae

❮ Previous
Next ❯

Citations

Apr 9, 2019·Expert Opinion on Emerging Drugs·Eun Ji ParkDong Hee Na
Jan 26, 2017·Frontiers in Pharmacology·Hong LiZhongmin Sun
Nov 7, 2019·International Journal of Molecular Sciences·Alberta BergamoGianni Sava

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bacterial Cell Wall Structure (ASM)

Bacterial cell walls are made of peptidoglycan (also called murein), which is made from polysaccharide chains cross-linked by unusual peptides containing D-amino acids. Here is the latest research on bacterial cell wall structures.

Bacterial Cell Wall Structure

Bacterial cell walls are made of peptidoglycan (also called murein), which is made from polysaccharide chains cross-linked by unusual peptides containing D-amino acids. Here is the latest research on bacterial cell wall structures.