Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 316K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Leteux, C. Articles by Ten Feizi Search for Related Content PubMed PubMed Citation Articles by Leteux, C. Articles by Ten Feizi, Social Bookmarking                            What's this?

Original Article

^a The Glycosciences Laboratory, Imperial College School of Medicine, Northwick Park Hospital, Harrow HA1 3UJ, United Kingdom
^b Laboratory of Molecular Structure, National Institute for Biological Standards and Control, Hertfordshire EN6 3QG, United Kingdom
^c Department of Biochemistry, Institute of Medical Biology, University of Tromsø, N-9037 Tromsø, Norway
^d Institut National de la Recherche Agronomique, Unit 1291, Station Physiologie de la Reproduction des Mammifères Domestiques, 37380 Nouzilly, France
^e Department of Molecular Immunology, The Rockefeller University, New York, New York 10021-6399
^f The Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10021-6399
The Glycosciences Laboratory, Imperial College School of Medicine, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.44-20-8869-345544-20-8869-3460

t.feizi{at}ic.ac.uk

The mannose receptor (MR) is an endocytic protein on macrophages and dendritic cells, as well as on hepatic endothelial, kidney mesangial, tracheal smooth muscle, and retinal pigment epithelial cells. The extracellular portion contains two types of carbohydrate-recognition domain (CRD): eight membrane-proximal C-type CRDs and a membrane-distal cysteine-rich domain (Cys-MR). The former bind mannose-, N-acetylglucosamine-, and fucose-terminating oligosaccharides, and may be important in innate immunity towards microbial pathogens, and in antigen trapping for processing and presentation in adaptive immunity. Cys-MR binds to the sulfated carbohydrate chains of pituitary hormones and may have a role in hormonal clearance. A second feature of Cys-MR is binding to macrophages in marginal zones of the spleen, and to B cell areas in germinal centers which may help direct MR-bearing cells toward germinal centers during the immune response. Here we describe two novel classes of carbohydrate ligand for Cys-MR: chondroitin-4 sulfate chains of the type found on proteoglycans produced by cells of the immune system, and sulfated blood group chains. We further demonstrate that Cys-MR interacts with cells in the spleen via the binding site for sulfated carbohydrates. Our data suggest that the three classes of sulfated carbohydrate ligands may variously regulate the trafficking and function of MR-bearing cells.

Key Words: chondroitin sulfate • cysteine-rich domain • lutropin (luteinizing hormone) • macrophage receptor • sulfo-Lewis^a/x

Abbreviations used in this paper: CRD, carbohydrate-recognition domain; CS, chondroitin sulfate; Cys-MR, cysteine-rich domain of the MR; UA, 4,5-unsaturated uronic acid; ECM, extracellular matrix; Hex, hexose; HexNAc, N-acetylhexosamine; IC₅₀, half-maximal inhibitory concentration; Ii, invariant chain; LNNT, lacto-N-neotetraose; LSIMS, liquid secondary ion mass spectrometry; MR, mannose receptor; NGL, neoglycolipid; pLH, porcine lutropin (luteinizing hormone); 3S-Le^a, 3'-sialyl-Lewis^a; 3S-Le^x, 3'-sialyl-Lewis^x; 3Su-Le^a, 3'-sulfated-Lewis^a; 3Su-Le^x, 3'-sulfated-Lewis^x; 6Su-Le^x, 6'-sulfated-Lewis^x; 3Su-LNNT, 3'-sulfated-LNNT; TBS, Tris-buffered saline.

© 2000 The Rockefeller University Press

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS