Salivary Agglutinin, Which Binds Streptococcus mutansand Helicobacter pylori, Is the Lung Scavenger Receptor Cysteine-rich Protein gp-340

Abstract

Salivary agglutinin is a high molecular mass component of human saliva that binds Streptococcus mutans, an oral bacterium implicated in dental caries. To study its protein sequence, we isolated the agglutinin from human parotid saliva. After trypsin digestion, a portion was analyzed by matrix-assisted laser/desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), which gave the molecular mass of 14 unique peptides. The remainder of the digest was subjected to high performance liquid chromatography, and the separated peptides were analyzed by MALDI-TOF/post-source decay; the spectra gave the sequences of five peptides. The molecular mass and peptide sequence information showed that salivary agglutinin peptides were identical to sequences in lung (lavage) gp-340, a member of the scavenger receptor cysteine-rich protein family. Immunoblotting with antibodies that specifically recognized either lung gp-340 or the agglutinin confirmed that the salivary agglutinin was gp-340. Immunoblotting with an antibody specific to the sialyl Le x carbohydrate epitope detected expression on the salivary but not the lung glycoprotein, possible evidence of different glycoforms. The salivary agglutinin also interacted with Helicobacter pylori, implicated in gastritis and peptic ulcer disease, Streptococcus agalactiae, implicated in neonatal meningitis, and several oral commensal streptococci. These results identify the salivary agglutinin as gp-340 and suggest it binds bacteria that are important determinants of either the oral ecology or systemic diseases.

Leucine-rich Repeats of Bacterial Surface Proteins Serve as Common Pattern Recognition Motifs of Human Scavenger Receptor gp340

“…The mechanisms of gp340 action in these different biological contexts are not known. Common to all scavenger receptors, the ligand repertoire of gp340 is wide; it binds many different types of bacteria as well as viruses (10,13,14). The wide ligand recognition pattern of scavenger receptors is thought to be based on the recognition of common microbial structures, such as lipopolysaccharides and lipoteichoic acids, but in the case of gp340, specific bacterial surface proteins are reported to be involved in the interactions characterized (15-18).…”

Effects of Muclin (Dmbt1) deficiency on the gastrointestinal system

“…Each group of investigators has given the gene/protein different names, and there are many proposed functions. The different names include Muclin (12), gp340 (31), salivary agglutinin (16,42), crp-ductin (6), ebnerin (29), hensin (54), vomeroglandin (33), and DMBT1 (37). We coined the name Muclin (mucin-like glycoprotein), which is based on the glycoprotein's biochemical characteristics (8).…”

“…It has also been detected weakly in the kidney and liver (53). DMBT1 gene expression in humans is strong in lung [weaker in mouse (12)]; at weak levels in brain (21,37); at strong levels in salivary glands (16,29,42); and at weak levels in mammary gland, uterus, testis, and prostate (21). In addition to these tissues, the protein has been detected in human tear fluid (48), sweat glands, hair follicles and epidermis (35), liver (47), alveolar macrophages (21), pancreatic juice (18), bile (28), and airway submucosal gland secretions (49).…”

“…The gp340 glycoprotein, expressed in salivary glands, airways, and genital tract, binds various bacterial pathogens and viruses (42,50,60,62). gp340 also binds to IgA (30) and the collectin surfactant protein D (32), both of which are known components of the innate immune defense system.…”

Identification of the Bacteria-binding Peptide Domain on Salivary Agglutinin (gp-340/DMBT1), a Member of the Scavenger Receptor Cysteine-rich Superfamily

“…SRCR proteins, e.g. the macrophage scavenger receptor, Mac-2-binding protein, CD5, CD6, WC1, Ebnerin, CRP (cyclic AMP receptor protein)-ductin, and lung gp-340, are associated with host defense systems (7,8,(11)(12)(13)(14)(15)(16)(17). Until now, studies dealing with agglutinin-bacteria interactions have been focused mainly on the characterization of bacterial receptors (18,19) and identification of their cognate carbohydrate ligands on agglutinin (1, 20 -22).…”