Chapter Thirteen - The Ashwell–Morell Receptor

Abstract

The Ashwell-Morell receptor (AMR) of hepatocytes, originally termed the hepatic asialoglycoprotein receptor, was the first cellular receptor to be identified and isolated and the first lectin to be detected in mammals. It is one of the multiple lectins of the C-type lectin family involved in recognition, binding, and clearance of asialoglycoproteins. We recently identified endogenous ligands of the AMR as desialylated prothrombotic components, including platelets and von Willebrand Factor [Ellies L. G., Ditto D., Levy G. G., Wahrenbrock M., Ginsburg D., Varki A., Le D. T., and Marth J. D. (2002). Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands. Proc. Natl. Acad. Sci. USA 99: pp. 10042-10047; Grewal, P. K. Uchiyama, S., Ditto, D., Varki, N., Le, D. T., Nizet, V., Marth, J. D. (2008). The Ashwell receptor mitigates the lethal coagulopathy of sepsis. Nat. Medicine 14, pp. 648-655]. Among these components, clearance by the liver's AMR is enhanced by exposure of terminal galactose on the glycan chains. A physiological role for engaging the AMR in rapid clearance was identified as mitigating disseminating intravascular coagulopathy in sepsis to promote survival. This chapter overviews the endogenous ligands of the AMR as components of the coagulatory system, describes clearance mechanisms of the liver, and details hematology and coagulation assays used in mouse coagulation studies.