Detoxification of Bacterial Lipopolysaccharides (Endotoxins) by a Human Neutrophil Enzyme

Lipopolysaccharides in the cell walls of Gram-negative bacteria elicit toxic as well as potentially beneficial inflammatory responses in animals. It is now reported that tissue toxicity caused by lipopolysaccharides is preferentially reduced by an enzymatic activity in human neutrophils. Acyloxyacyl...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1986-10, Vol.234 (4773), p.203-205
Main Authors: Munford, Robert S., Hall, Catherine L.
Format: Article
Language:English
Subjects:
Animals
B lymphocytes
Bacteria
Bacteriology
Biochemistry
Biological and medical sciences
Carboxylic Ester Hydrolases - blood
Enzymes
Fatty acids
Fundamental and applied biological sciences. Psychology
Humans
Hydrolysis
Lipid A - metabolism
Lipid A - pharmacology
Lipid A - toxicity
Lipids
Lipopolysaccharides
Lipopolysaccharides - metabolism
Lipopolysaccharides - pharmacology
Lipopolysaccharides - toxicity
Lymphocyte Activation
Medical research
Microbiology
Molecules
Neutrophils
Neutrophils - enzymology
Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains
Rabbits
Radioactive decay
Salmonella typhimurium
Shwartzman Phenomenon
Toxicity
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Summary:Lipopolysaccharides in the cell walls of Gram-negative bacteria elicit toxic as well as potentially beneficial inflammatory responses in animals. It is now reported that tissue toxicity caused by lipopolysaccharides is preferentially reduced by an enzymatic activity in human neutrophils. Acyloxyacyl hydrolysis removes fatty acyl chains that are linked to the hydroxyl groups of 3-hydroxytetradecanoyl residues in the bioactive lipid A moiety of the lipopolysaccharides. Maximal acyloxyacyl hydrolysis reduced lipopolysaccharide tissue toxicity, as measured in the dermal Shwartzman reaction, by a factor of 100 or more. In contrast, the ability of the deacylated lipopolysaccharides to stimulate B lymphocytes to divide was decreased only by a factor of 12. It is suggested that during tissue invasion by Gram-negative bacteria acyloxyacyl hydrolysis may be a defense mechanism that reduces the toxicity of lipopolysaccharides while preserving some of their potentially beneficial inflammatory and immune stimuli.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.3529396