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Science 8 March 2002:
Vol. 295. no. 5561, pp. 1898 - 1901
DOI: 10.1126/science.1069540
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Reports

Mannose Receptor-Mediated Regulation of Serum Glycoprotein Homeostasis

Sena J. Lee,1 Stefan Evers,2 Daniel Roeder,3 Albert F. Parlow,4 Juha Risteli,5 Leila Risteli,5 Y. C. Lee,6 Ten Feizi,7 Hanno Langen,23 Michel C. Nussenzweig18*

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.

1 Laboratory of Molecular Immunology, The Rockefeller University, 1230 York Avenue, Box #220, New York, NY 10021, USA.
2 Infectious Diseases,
3 Genetics, F. Hoffmann-La Roche, CH-4070 Basel, Switzerland.
4 National Hormone and Pituitary Program, Harbor-University of California-Los Angeles Medical Center, Torrance, CA 90509, USA.
5 Department of Clinical Chemistry, University of Oulu, Oulu FIN-90014, Finland.
6 Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
7 Glycosciences Laboratory. Imperial College of Science Technology and Medicine, Faculty of Medicine, Northwick Park Institute for Medical Research, Harrow, HA1 3UJ, UK.
8 Howard Hughes Medical Institute, New York, NY 10021, USA.
*   To whom correspondence should be addressed. E-mail: nussen{at}mail.rockefeller.edu

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