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Monoclonal antibody to mouse lipopolysaccharide receptor protects mice against the lethal effects of endotoxin
D C Morrison1, R Silverstein, S W Bright
1Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City 66103.
Abstract:
Specific endotoxic lipopolysaccharide (LPS) binding sites on the cell membranes of murine lymphocytes and macrophages that may serve as functional receptors for LPS have recently been identified using photoactivatable cross-linking LPS derivatives. A monoclonal antibody (Mab 5D3) with specificity for this 80-kDa protein has also been generated and characterized. The capacity of MAb 5D3 to protect mice against the lethal effects of endotoxin was investigated. Pretreatment of CF1 mice with as little as 15 micrograms of MAb 5D3 provided virtually complete protection against a dose of endotoxin 10-fold greater than that required to kill all mice in an untreated control group using the galactosamine sensitization model. Significant protection was also afforded normal mice given MAb 5D3 relative to saline. Several lines of evidence suggest that MAb 5D3-mediated protection is due to the agonist properties of this antibody rather than a receptor blockade mechanism.
Insights
A new monoclonal antibody (Mab 5D3) protects mice from lethal endotoxin effects. This antibody acts as an agonist, targeting specific lipopolysaccharide (LPS) binding sites on immune cells, offering significant protection.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Endotoxic lipopolysaccharide (LPS) binding sites on murine lymphocytes and macrophages are potential functional receptors.
- Photoactivatable cross-linking LPS derivatives identified these specific 80-kDa protein binding sites.
- A monoclonal antibody, Mab 5D3, was generated targeting this 80-kDa protein.
Purpose of the Study:
- To investigate the protective capacity of Mab 5D3 against lethal endotoxin effects in mice.
- To determine if Mab 5D3 acts via receptor blockade or agonist properties.
Main Methods:
- Pretreatment of CF1 mice with Mab 5D3 before endotoxin administration.
- Utilizing the galactosamine sensitization model to assess endotoxin lethality.
- Comparing protection afforded by Mab 5D3 versus saline in normal mice.
Main Results:
- 15 micrograms of Mab 5D3 provided nearly complete protection against a 10-fold higher lethal dose of endotoxin.
- Significant protection was observed in normal mice treated with Mab 5D3 compared to saline controls.
- Evidence suggests Mab 5D3-mediated protection is due to agonist properties.
Conclusions:
- Mab 5D3 demonstrates significant efficacy in protecting mice against endotoxin-induced lethality.
- The protective mechanism of Mab 5D3 appears to be agonistic rather than receptor blockade.
- These findings highlight Mab 5D3 as a potential therapeutic agent for endotoxin-related conditions.