Back to Search
Start Over
The low density receptor-related protein 1 plays a significant role in ricin-mediated intoxication of lung cells
- Source :
- Scientific Reports, Scientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group UK, 2020.
-
Abstract
- Ricin, a highly lethal plant-derived toxin, is a potential biological threat agent due to its high availability, ease of production and the lack of approved medical countermeasures for post-exposure treatment. To date, no specific ricin receptors were identified. Here we show for the first time, that the low density lipoprotein receptor-related protein-1 (LRP1) is a major target molecule for binding of ricin. Pretreating HEK293 acetylcholinesterase-producer cells with either anti-LRP1 antibodies or with Receptor-Associated Protein (a natural LRP1 antagonist), or using siRNA to knock-down LRP1 expression resulted in a marked reduction in their sensitivity towards ricin. Binding assays further demonstrated that ricin bound exclusively to the cluster II binding domain of LRP1, via the ricin B subunit. Ricin binding to the cluster II binding domain of LRP1 was significantly reduced by an anti-ricin monoclonal antibody, which confers high-level protection to ricin pulmonary-exposed mice. Finally, we tested the contribution of LRP1 receptor to ricin intoxication of lung cells derived from mice. Treating these cells with anti-LRP1 antibody prior to ricin exposure, prevented their intoxication. Taken together, our findings clearly demonstrate that the LRP1 receptor plays an important role in ricin-induced pulmonary intoxications.
- Subjects :
- 0301 basic medicine
endocrine system
Cell biology
medicine.drug_class
lcsh:Medicine
Mice, Inbred Strains
Ricin
Monoclonal antibody
medicine.disease_cause
Biochemistry
Article
Antibodies
Mass Spectrometry
03 medical and health sciences
chemistry.chemical_compound
medicine
Animals
Humans
lcsh:Science
Receptor
Lung
Multidisciplinary
Microscopy, Confocal
030102 biochemistry & molecular biology
biology
Toxin
lcsh:R
HEK 293 cells
Membrane Proteins
Molecular biology
LRP1
Antibodies, Neutralizing
carbohydrates (lipids)
enzymes and coenzymes (carbohydrates)
030104 developmental biology
HEK293 Cells
chemistry
Gene Knockdown Techniques
biology.protein
Acetylcholinesterase
lcsh:Q
Female
Antibody
Low Density Lipoprotein Receptor-Related Protein-1
Binding domain
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....a38719aaeb31018a65f37ca302837068