Lipoprotein-bound endotoxin exerts an immunomodulatory effect on hepatocytes through the lipid A domain of LPS
| Autor: | Karl H. Weisgraber, D.H. Lee, Hobart W. Harris, F. Behzad Kasravi |
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| Rok vydání: | 2005 |
| Předmět: |
Innate immune system
Lipopolysaccharide medicine.medical_treatment Immunology Cell Biology Biology Microbiology Nitric oxide Lipid A chemistry.chemical_compound Infectious Diseases Cytokine chemistry Biochemistry Toxicity medicine lipids (amino acids peptides and proteins) Molecular Biology Lipoprotein Chylomicron |
| Zdroj: | Journal of Endotoxin Research. 11:19-24 |
| ISSN: | 0968-0519 |
| DOI: | 10.1177/09680519050110010601 |
| Popis: | Background: We have previously shown that chylomicron (CM)-bound lipopolysaccharide (LPS) inhibits the host innate immune response by rendering hepatocytes tolerant to pro-inflammatory cytokine stimulation. However, LPS is a complex macromolecule containing both lipid and carbohydrate domains. We hypothesized that just as lipid A confers the toxicity of LPS, it is also responsible for the immunoregulatory effect on hepatocytes. Methods: We pretreated primary rat hepatocytes for 2 h with a series of CM-LPS complexes in which the endotoxin moiety varied in its structure and/or toxicity. Subsequently, the cells were stimulated with a mixture of pro-inflammatory cytokines. Nitric oxide production was measured as an indicator of hepatocellular activation. Results: All pretreatments wherein the CM-bound complex contained the lipid A moiety readily inhibited the hepatocellular cytokine response, including CM bound to lipid A alone. In contrast, CM-LPS complexes containing detoxified LPS, which lacks the lipid A domain, had no effect on the hepatocellular response to cytokines. Conclusions: The lipid A domain of the LPS macromolecule is both sufficient and essential for the CM-mediated induction of cytokine tolerance in hepatocytes. However, this process is independent of the specific endotoxic activity of the lipid A moiety. |
| Databáze: | OpenAIRE |
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