Effect of O-antigenic polysaccharide of Escherichia coli on endotoxin neutralizing activity of lysozyme.
Endotoxemia is considered to be associated with the high mortality of gram-negative septic patients. Increasing evidence shows that beta-lactam antibiotics have a propensity to induce endotoxin release from the bacterial outer membrane while killing bacteria. We have recently found that egg white lysozyme (EW-LZM) shows strong inhibition of beta-lactam induced bacteriolysis and lipopolysaccharide (LPS) release from Escherichia coli O111, resulting in reduction of the LPS-initiated inflammatory response. In this study, we compared the effect of EW-LZM on E. coli J5, which possesses rough-type LPS (RaLPS), in order to demonstrate the effect of O-antigenic polysaccharide on endotoxin neutralizing activity of EW-LZM and on inhibition of beta-lactam induced lysis by LZM. Both of the beta-lactam induced bacterial lysis and subsequent LPS release were almost completely inhibited by EW-LZM. The effect was more potent than that of wild-type LPS as assessed by released LPS concentration and LPS induced cytokine syntheses. In addition, EW-LZM was effective against lethal infection of E. coli J5 in cyclophosphamide induced leukopenic mice. These facts strongly suggested that O-antigenic polysaccharide negatively modulates LPS neutralizing activity of EW-LZM.
Liang
A H
AH
Lab. Immunopharm. Microb. Prod., School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Sugawara
N
N
Ohno
N
N
Adachi
Y
Y
Yadomae
T
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001433:Bacteriolysis / Q000187:drug effects; D002351:Carrageenan / Q000494:pharmacology; D002460:Cell Line; D003520:Cyclophosphamide / Q000494:pharmacology; D004195:Disease Models, Animal; D019446:Endotoxemia; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology*; D005690:Galactose / Q000494:pharmacology; D007769:Lactams; D007970:Leukopenia / Q000139:chemically induced; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015846:Monokines / Q000378:metabolism; D009113:Muramidase / Q000494:pharmacology*; D019081:O Antigens
D000900:Anti-Bacterial Agents; D004731:Endotoxins; D007769:Lactams; D008070:Lipopolysaccharides; D015846:Monokines; D019081:O Antigens; D003520:Cyclophosphamide; D002351:Carrageenan; D009113:Muramidase; D005690:Galactose