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The Low Density Receptor-Related Protein 1 Plays a Significant Role in Ricin-Mediated Intoxication of Lung Cells

Reut Falach, Anita Sapoznikov, Yoav Gal, Eytan Elhanany, Yentl Evgy, Ohad Shifman, Moshe Aftalion, Sharon Ehrlich, Shlomi Lazar, Tamar Sabo, Chanoch Kronman, Ohad Mazor

Sci Rep. 2020 Jun 2;10(1):9007.

PMID: 32488096

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR4247993 Monoclonal Anti-LRP1 antibody produced in mouse Monoclonal Anti-LRP1 antibody produced in mouse Price
IAR4248017 Anti-LRP1 antibody produced in mouse Anti-LRP1 antibody produced in mouse Price
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