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Complement activation by salivary agglutinin is secretor status dependent

  • Sabrina T.G. Gunput EMAIL logo , Antoon J.M. Ligtenberg , Bas Terlouw , Mieke Brouwer , Enno C.I. Veerman and Diana Wouters
Published/Copyright: July 24, 2014
Biological Chemistry
From the journal Biological Chemistry Volume 396 Issue 1

Abstract

After mucosal damage or gingival inflammation, complement proteins leak into the oral cavity and mix with salivary proteins such as salivary agglutinin (SAG/gp-340/DMBT1). This protein is encoded by the gene Deleted in Malignant Brain Tumors 1 (DMBT1), and it aggregates bacteria, viruses and fungi, and activates the lectin pathway of the complement system. In the lectin pathway, carbohydrate structures on pathogens or altered self cells are recognized. SAG is highly glycosylated, partly on the basis of the donor’s blood group status. Whereas secretors express Lewis b, Lewis y, and antigens from the ABO-blood group system on SAG, non-secretors do not. Through mannose-binding lectin (MBL) binding and C4 deposition assays, we aimed to identify the chemical structures on SAG that are responsible for complement activation. The complement-activating properties of SAG were completely abolished by oxidation of its carbohydrate moiety. SAG-mediated activation of complement was also inhibited in the presence of saccharides such as fucose and Lewis b carbohydrates, and also after pretreatment with the fucose-binding lectin, Anguilla anguilla agglutinin. Complement activation was significantly (p<0.01) higher in secretors than in non-secretors. Our results suggest that fucose-rich oligosaccharide sidechains, such as Lewis b antigens, are involved in the activation of complement by SAG.

Keywords: DMBT1; innate immunity; Lewis antigens; mannose-binding lectin; saliva
Corresponding author: Sabrina T.G. Gunput, Academic Centre for Dentistry Amsterdam (ACTA), Department of Oral Biochemistry, Free University and University of Amsterdam, Gustav Mahlerlaan 3004, NL-1081 LA Amsterdam, The Netherlands, e-mail:

Acknowledgments

We wish to thank Dr. E.A. Nicu and W.J. Teeuw for their assistance in obtaining serum samples.

Conflict of interest statement

Disclosure statement: The authors have no financial conflict of interest.

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Supplemental Material

The online version of this article (DOI: 10.1515/hsz-2014-0200) offers supplementary material, available to authorized users.

Received: 2014-5-22
Accepted: 2014-7-20
Published Online: 2014-7-24
Published in Print: 2015-1-1

©2014 by De Gruyter

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https://doi.org/10.1515/hsz-2014-0200
Keywords for this article
DMBT1; innate immunity; Lewis antigens; mannose-binding lectin; saliva

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Cholesterol lowering: role in cancer prevention and treatment
  4. The role of the Mpv17 protein mutations of which cause mitochondrial DNA depletion syndrome (MDDS): lessons from homologs in different species
  5. Research Articles/Short Communications
  6. Genes and Nucleic Acids
  7. Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing
  8. Protein Structure and Function
  9. Complement activation by salivary agglutinin is secretor status dependent
  10. Synthesis, biological evaluation, and docking studies of PAR2-AP-derived pseudopeptides as inhibitors of kallikrein 5 and 6
  11. Membranes, Lipids, Glycobiology
  12. Recombinant HDL (Milano) protects endotoxin-challenged rats from multiple organ injury and dysfunction
  13. Cell Biology and Signaling
  14. miR-126 regulates platelet-derived growth factor receptor-α expression and migration of primary human osteoblasts
  15. Legumain expression, activity and secretion are increased during monocyte-to-macrophage differentiation and inhibited by atorvastatin
  16. Proteolysis
  17. Cell surface serine protease matriptase-2 suppresses fetuin-A/AHSG-mediated induction of hepcidin
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