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Glycobiology Advance Access originally published online on November 10, 2005
Glycobiology 2006 16(3):237-243; doi:10.1093/glycob/cwj058
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

LacdiNAc- and LacNAc-containing glycans induce granulomas in an in vivo model for schistosome egg-induced hepatic granuloma formation

Koen K. Van de Vijver2,3, André M. Deelder2, Werner Jacobs3, Eric A. Van Marck3 and Cornelis H. Hokke1,2

2 Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands; and 3 Department of Pathology, Antwerp University, Universiteitsplein 1, B-2610 Antwerp, Belgium

1To whom correspondence should be addressed; e-mail: c.h.hokke{at}lumc.nl

Received on September 30, 2005; revised on November 7, 2005; accepted on November 8, 2005

Schistosomes, major parasitic helminths, express numerous glycoconjugates that provoke humoral and cellular immune responses in the infected human host. The main pathology in schistosomiasis is due to the formation of granulomas around tissue-trapped eggs and the resulting organ damage. By using a mouse model of induction of granulomas by hepatic implantation of antigen-coated beads, it has been determined that the glycan part of schistosomal soluble egg antigens (SEA) initiates granulomogenesis. To identify which individual glycan elements in this complex SEA mixture are granulomogenic, we have tested in the same mouse model conjugates of various synthetic oligosaccharides characteristic for schistosome eggs, including GalNAcß1-4GlcNAc (LacdiNAc, LDN), Galß1-4(Fuc{alpha}1-3)GlcNAc (Lewisx), Fuc{alpha}1-2Fuc{alpha}1-3GlcNAc (DF-Gn), and Fuc{alpha}1-3GalNAcß1-4(Fuc{alpha}1-3)GlcNAc (F-LDN-F). Ribonuclease (RNase) A and B, and different fetuin glycoforms were included as controls. Only beads that carry glycoconjugates with terminal LacdiNAc or Galß1-4GlcNAc (LacNAc, LN) elements gave rise to granulomas, with macrophage, lymphocyte, and eosinophil levels similar to the granulomatous lesions caused by schistosome eggs in a natural infection. Uncoated beads, and beads coated with fucosylated glycoconjugates or glycoconjugates lacking terminally exposed Gal or GalNAc, only attracted a monolayer of macrophages. These results indicate that the formation of hepatic granulomas is triggered specifically by glycoconjugates which carry terminal LacNAc or LacdiNAc, both constituents of the schistosome egg.

Key words: carbohydrate antigen / galectin / hepatic granulomas / schistosomiasis


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