Mannose Receptor-Mediated Regulation of Serum Glycoprotein Homeostasis

Sena J. Lee(Rockefeller University), Stefan Evers(Office of Infectious Diseases), Daniel Roeder(Roche (Switzerland)), Albert F. Parlow(UCLA Medical Center), Juha Risteli(University of Oulu), Leila Risteli(University of Oulu), Y. C. Lee(Johns Hopkins University), Ten Feizi(Northwick Park Institute for Medical Research), Hanno Langen(Roche (Switzerland)), Michel C. Nussenzweig(Howard Hughes Medical Institute)
Science
March 8, 2002
10.1126/science.1069540
Cited by 481

Abstract

Carbohydrates are thought to function as tags that mark circulatory glycoproteins for rapid clearance. To examine the role of the mannose receptor (MR) in glycoprotein clearance, we generated mice genetically deficient in MR. MR-/- mice were defective in clearing proteins bearing accessible mannose and N-acetylglucosamine residues and had elevated levels of eight different lysosomal hydrolases. Proteomic analysis of MR-/- and control mouse sera showed that an additional 4 out of 52 proteins identified were elevated in MR-/- serum. Each of these is up-regulated during inflammation and wound healing. Thus, MR appears to operate as an essential regulator of serum glycoprotein homeostasis.

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