Highly glycosylated human salivary molecules present oligosaccharides that mediate adhesion of leukocytes and Helicobacter pylori.
Glycoproteins display carbohydrate facets that serve as adhesion receptors for cells including leukocytes and bacterial cells. Our aim was to understand the role of the specialized carbohydrate motifs carried by highly glycosylated human salivary proteins in regulating the oral ecology. To date, our structural studies suggest that these molecules display a wide array of oligosaccharide structures, including many species with highly charged and/or fucosylated termini. Here, we used an immunoblot approach to gain additional information about the nature of these oligosaccharides. The results showed that MG1 and the salivary agglutinin express the MECA-79 epitope, an unusual sulfated carbohydrate structure that belongs to an important class of high-affinity (endothelial) L-selectin ligands. Unexpectedly, we discovered that in many women the expression of this epitope is hormonally regulated. Additional experiments revealed that MG1, MG2, and the salivary agglutinin also present Lewis blood group antigens, the exact repertoire varying on an individual basis. In parallel, we explored the functions of these carbohydrate motifs. Using an assay that detects L-selectin ligands, we found that the subset of MECA-79-reactive oligosaccharides displayed on salivary molecules specifically bind an L-selectin/Fc chimera. In contrast, the Lewis blood group structures are receptors for many strains of Helicobacter pylori, an organism that is implicated in the development of gastric ulcers and cancer. Together, these results suggest that MG1, MG2, and the salivary agglutinin play important roles in governing leukocyte and bacterial adhesion. Our findings suggest novel strategies, based on the relevant carbohydrate structures, for promoting or inhibiting these processes.
Prakobphol
Akraporn
A
Departments of Stomatology, University of California, San Francisco, California 94143, USA.
Borén
Thomas
T
Ma
Wenge
W
Zhixiang
Peng
P
Fisher
Susan J
SJ
D000328:Adult; D000368:Aged; D001422:Bacterial Adhesion / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology; D000939:Epitopes / Q000096:biosynthesis / Q000502:physiology; D005260:Female; D006031:Glycosylation; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D019041:L-Selectin / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism / Q000382:microbiology / Q000502:physiology*; D007983:Lewis Blood Group Antigens / Q000096:biosynthesis / Q000502:physiology; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000378:metabolism / Q000382:microbiology / Q000502:physiology; D055257:Mucin-5B; D009077:Mucins / Q000096:biosynthesis / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D012471:Salivary Proteins and Peptides / Q000378:metabolism* / Q000502:physiology; D012727:Sex Characteristics
D000939:Epitopes; D007983:Lewis Blood Group Antigens; D008024:Ligands; C524578:MUC5B protein, human; D055257:Mucin-5B; D009077:Mucins; D009844:Oligosaccharides; D012471:Salivary Proteins and Peptides; D019041:L-Selectin