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dc.contributor.authorSwystun, Laura L.
dc.contributor.authorOgiwara, Kenichi
dc.contributor.authorLai, Jesse D.
dc.contributor.authorOjala, Juha R. M.
dc.contributor.authorRawley, Orla
dc.contributor.authorLassalle, Fanny
dc.contributor.authorNotley, Colleen
dc.contributor.authorRengby, Olle
dc.contributor.authorMichels, Alison
dc.contributor.authorNesbitt, Kate
dc.contributor.authorTryggvason, Karl
dc.contributor.authorLillicrap, David
dc.date.accessioned2019-07-09T16:12:06Z
dc.date.available2019-07-09T16:12:06Z
dc.date.issued2019-05-24
dc.identifier.citationSwystun, L. L., Ogiwara, K., Lai, J. D., Ojala, J. R. M., Rawley, O., Lassalle, F., … Lillicrap, D. (2019). The scavenger receptor SCARA 5 is an endocytic receptor for von Willebrand factor expressed by littoral cells in the human spleen. Journal of Thrombosis and Haemostasis. doi:10.1111/jth.14521en
dc.identifier.urihttp://hdl.handle.net/1974/26372
dc.descriptionThis is the peer reviewed version of the following article: Swystun, L. L., Ogiwara, K., Lai, J. D., Ojala, J. R. M., Rawley, O., Lassalle, F., … Lillicrap, D. (2019). The scavenger receptor SCARA 5 is an endocytic receptor for von Willebrand factor expressed by littoral cells in the human spleen. Journal of Thrombosis and Haemostasis. doi:10.1111/jth.14521, which has been published in final form at http://dx.doi.org/10.1111/jth.14521. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.en
dc.description.abstractBackground Scavenger receptors play a significant role in clearing aged proteins from the plasma, including the large glycoprotein coagulation factors von Willebrand factor (VWF) and factor VIII (FVIII). A large genome-wide association study meta-analysis has identified genetic variants in the gene SCARA5, which encodes the class A scavenger receptor SCARA5, as being associated with plasma levels of VWF and FVIII. Objectives The ability of SCARA5 to regulate the clearance of VWF-FVIII was characterized. Methods VWF-FVIII interactions with SCARA5 were evaluated by solid phase binding assays and in vitro cell based assays. The influence of SCARA5 deficiency on VWF:Ag and half-life was assessed in a murine model. The expression pattern of SCARA5 and its colocalization with VWF was evaluated in human tissues. Results VWF and the VWF-FVIII complex bound to human recombinant SCARA5 in a dose- and calcium-dependent manner. SCARA5 expressing HEK 293T cells bound and internalized VWF and the VWF-FVIII complex into early endosomes. In vivo, SCARA5 deficiency had a modest influence on the half-life of human VWF. mRNA analysis and immunohistochemistry determined that human SCARA5 is expressed in kidney podocytes and the red pulp, white pulp, and marginal zone of the spleen. VWF was found to colocalize with SCARA5 expressed by littoral cells lining the red pulp of the human spleen. Conclusions SCARA5 is an adhesive and endocytic receptor for VWF. In human tissues, SCARA5 is expressed by kidney podocytes and splenic littoral endothelial cells. SCARA5 may have a modest influence on VWF clearance in humans.en
dc.publisherWileyen
dc.subjectendocytosisen
dc.subjectendothelial cellsen
dc.subjectfactor VIIIen
dc.subjectGWASen
dc.subjectreceptors scavengeren
dc.subjectvon Willebrand factoren
dc.titleThe scavenger receptor SCARA5 is an endocytic receptor for von Willebrand factor expressed by littoral cells in the human spleenen
dc.typejournal articleen
dc.identifier.doihttps://dx.doi.org/10.1111/jth.14521


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