Lipopolysaccharide from Rhodobacter sphaeroides is an agonist in equine cells.
Abstract: Endotoxemia is associated with the principal causes of death in adult horses and equine neonates and, therefore, veterinary researchers are expending efforts to identify new therapeutic interventions that might be beneficial in these animals. Endotoxin antagonists inhibit interaction of endotoxin with cellular receptors and may be beneficial in the treatment of endotoxemia and sepsis. Diphosphoryl lipid A from Rhodobacter sphaeroides (RsDPLA) is a potent antagonist of enteric LPS in human cells, but is an agonist in hamster cells. In this study, the effect of lipopolysaccharide from R. sphaeroides (RsLPS) on equine whole blood and isolated monocyte preparations was investigated by comparing tumor necrosis factor (TNF) production in response to RsLPS and Escherichia coli O55:B5 LPS. Our results indicate that RsLPS is a potent agonist in equine cells, which precludes therapeutic use of this agent in equine patients. In contrast to the results in equine cells, RsLPS did not elicit TNF production by itself, and inhibited the response to E. coli O55:B5 LPS in a human monocytic cell line.
Publication Date: 2003-04-15 PubMed ID: 12691616DOI: 10.1179/096805103125001315Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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This research explores the effect of the lipopolysaccharide from Rhodobacter sphaeroides (RsLPS) on equine blood and monocyte cells, and finds it to be detrimental rather than therapeutic in treating endotoxemia and sepsis in horses.
Research Objective
- The main objective of this study was to evaluate the effect of lipopolysaccharide from R. sphaeroides (RsLPS) on equine cells. Endotoxemia is a major contributor to mortality in adult horses and neonates. As a result, controlling it using endotoxin antagonists is a key research area in veterinary medicine. Importantly, RsLPS has been found to have varied effects on different species, acting as an antagonist in human cells and an agonist in hamster cells.
Methodology
- The researchers studied the effect of RsLPS on equine whole blood and isolated monocyte preparations. This was done by comparing the production of tumor necrosis factor (TNF) in response to RsLPS and E. coli O55:B5 LPS.
Results
- The results indicated that RsLPS is a potent agonist in equine cells, meaning that it triggers an active response rather than softening or negating the impact of endotoxins.
- This finding contradicts its function in humans, where RsLPS has an inhibitory effect on the response of a human monocytic cell line to E. Coli O55:B5 LPS, and does not trigger TNF production by itself.
Implications
- These results demonstrate that RsLPS cannot be used therapeutically in horses. While it may work as an endotoxin antagonist in humans, its strong agonist action in equine cells will likely worsen rather than ameliorate health conditions related to endotoxemia.
- The study highlights the importance of investigating species-specific responses when designing and evaluating potential therapeutic interventions.
Cite This Article
APA
Lohmann KL, Vandenplas M, Barton MH, Moore JN.
(2003).
Lipopolysaccharide from Rhodobacter sphaeroides is an agonist in equine cells.
J Endotoxin Res, 9(1), 33-37.
https://doi.org/10.1179/096805103125001315 Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
MeSH Terms
- Animals
- Dose-Response Relationship, Immunologic
- Escherichia coli / immunology
- Horses / blood
- Humans
- Leukocytes, Mononuclear / drug effects
- Leukocytes, Mononuclear / metabolism
- Lipid A / analogs & derivatives
- Lipid A / pharmacology
- Lipopolysaccharides / pharmacology
- Rhodobacter sphaeroides
- Species Specificity
- Tumor Necrosis Factor-alpha / biosynthesis
Citations
This article has been cited 10 times.- Dobrovolskaia MA. Pre-clinical immunotoxicity studies of nanotechnology-formulated drugs: Challenges, considerations and strategy. J Control Release 2015 Dec 28;220(Pt B):571-83.
- Lonez C, Irvine KL, Pizzuto M, Schmidt BI, Gay NJ, Ruysschaert JM, Gangloff M, Bryant CE. Critical residues involved in Toll-like receptor 4 activation by cationic lipid nanocarriers are not located at the lipopolysaccharide-binding interface. Cell Mol Life Sci 2015 Oct;72(20):3971-82.
- Anwar MA, Panneerselvam S, Shah M, Choi S. Insights into the species-specific TLR4 signaling mechanism in response to Rhodobacter sphaeroides lipid A detection. Sci Rep 2015 Jan 7;5:7657.
- Irvine KL, Gangloff M, Walsh CM, Spring DR, Gay NJ, Bryant CE. Identification of key residues that confer Rhodobacter sphaeroides LPS activity at horse TLR4/MD-2. PLoS One 2014;9(5):e98776.
- Scior T, Alexander C, Zaehringer U. Reviewing and identifying amino acids of human, murine, canine and equine TLR4 / MD-2 receptor complexes conferring endotoxic innate immunity activation by LPS/lipid A, or antagonistic effects by Eritoran, in contrast to species-dependent modulation by lipid IVa. Comput Struct Biotechnol J 2013;5:e201302012.
- Cheng BH, Chan JY, Chan BC, Lin HQ, Han XQ, Zhou X, Wan DC, Wang YF, Leung PC, Fung KP, Lau CB. Structural characterization and immunomodulatory effect of a polysaccharide HCP-2 from Houttuynia cordata. Carbohydr Polym 2014 Mar 15;103:244-9.
- Bryant CE, Monie TP. Mice, men and the relatives: cross-species studies underpin innate immunity. Open Biol 2012 Apr;2(4):120015.
- Werners AH, Bryant CE. Pattern recognition receptors in equine endotoxaemia and sepsis. Equine Vet J 2012 Jul;44(4):490-8.
- Bryant CE, Spring DR, Gangloff M, Gay NJ. The molecular basis of the host response to lipopolysaccharide. Nat Rev Microbiol 2010 Jan;8(1):8-14.
- Bryant CE, Ouellette A, Lohmann K, Vandenplas M, Moore JN, Maskell DJ, Farnfield BA. The cellular Toll-like receptor 4 antagonist E5531 can act as an agonist in horse whole blood. Vet Immunol Immunopathol 2007 Apr 15;116(3-4):182-9.
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