The Human Glycoprotein Salivary Agglutinin Inhibits the Interaction of DC-SIGN and Langerin with Oral Micro-Organisms

Boks, Martine A.; Gunput, Sabrina T.G.; Kosten, Ilona; Gibbs, Susan; Vliet, Sandra J. van; Ligtenberg, A.J.M.; Kooyk, Yvette van

doi:10.1159/000443016

Cited by 10 publications

(6 citation statements)

References 46 publications

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“…On the one hand, it is able to aggregate Streptococcus mutans and S. sanguis as well as influenza A virus (maybe via its SRCR domains) promoting their clearance from the oral cavity [2,67]. On the other hand, DMBT1 gp340 probably interacts via its mannose and fucose structures with the C-type lectin receptors DC-SIGN and Langerin, which prevented binding of Candida albicans and Escheria coli to these receptors [70]. Furthermore, DMBT1 gp340 binds to a variety of host proteins, such as surfactant proteins, lactoferrin, MUC5B, galectin 3, and even TFF2 [67,71].…”

Section: Potential Role Of Salivary Tff3mentioning

confidence: 99%

Salivary Trefoil Factor Family (TFF) Peptides and Their Roles in Oral and Esophageal Protection: Therapeutic Potential

Hoffmann

2021

IJMS

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Human saliva is a complex body fluid with more than 3000 different identified proteins. Besides rheological and lubricating properties, saliva supports wound healing and acts as an antimicrobial barrier. TFF peptides are secreted from the mucous acini of the major and minor salivary glands and are typical constituents of normal saliva; TFF3 being the predominant peptide compared with TFF1 and TFF2. Only TFF3 is easily detectable by Western blotting. It occurs in two forms, a disulfide-linked homodimer (Mr: 13k) and a high-molecular-mass heterodimer with IgG Fc binding protein (FCGBP). TFF peptides are secretory lectins known for their protective effects in mucous epithelia; the TFF3 dimer probably has wound-healing properties due to its weak motogenic effect. There are multiple indications that FCGBP and TFF3-FCGBP play a key role in the innate immune defense of mucous epithelia. In addition, homodimeric TFF3 interacts in vitro with the salivary agglutinin DMBT1gp340. Here, the protective roles of TFF peptides, FCGBP, and DMBT1gp340 in saliva are discussed. TFF peptides are also used to reduce radiotherapy- or chemotherapy-induced oral mucositis. Thus, TFF peptides, FCGBP, and DMBT1gp340 are promising candidates for better formulations of artificial saliva, particularly improving wound healing and antimicrobial effects even in the esophagus.

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Section: Potential Role Of Salivary Tff3mentioning

confidence: 99%

Salivary Trefoil Factor Family (TFF) Peptides and Their Roles in Oral and Esophageal Protection: Therapeutic Potential

Hoffmann

2021

IJMS

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“…Salivary agglutinin (SAG), a major AMP in saliva, promotes microbial agglutination to facilitate microbial clearance, which provides protection against pathogen infection (Gunput et al 2016;Reichhardt et al 2017;Reichhardt and Meri 2016;Sonesson et al 2011;Zhang et al 2019b). Moreover, SAG can also elevate pathogen removal by competitively inhibiting microbial colonization to host cells (Boks et al 2016). In addition, SAG is able to bind endogenous molecules, such as lactoferrin, secretory immune globulin (Ig) A, and surfactant proteins A and D, to increase antimicrobial effects in a synergistic action (Hartshorn et al 2006;Madsen et al 2010;Reichhardt et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Oral antimicrobial activity weakened in children with electronic waste lead exposure

Zhang

Huo

et al. 2020

Environ Sci Pollut Res

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Environmental lead (Pb) exposure can induce dysbacteriosis, impair oral health, and is associated with the development of dental caries. However, the mechanism is unclear. The aim of this study was to explore the effects of Pb toxicity on oral antimicrobial activity in children in an e-waste area. Results showed higher blood Pb levels in e-waste-exposed group children, accompanied by decreased saliva SAG (salivary agglutinin) concentrations, increased peripheral WBC (white blood cell) counts and monocyte counts, and elevated peripheral monocyte percentage. LnPb (natural logarithmic transformation of blood Pb level) was negatively correlated with saliva SAG concentration, while positively correlated with peripheral monocyte percentage. Saliva SAG concentration played a complete mediating role in the correlation of LnPb to peripheral monocyte percentage. To our knowledge, this is the first study on the relationship of environmental Pb exposure and oral antimicrobial activity in children, showing that environmental Pb exposure may weaken oral antimicrobial activity through reducing saliva SAG concentration, which may raise the risk of oral dysbacteriosis and ultimately pathogen infection. Keywords Oral antimicrobial activity . Children . Lead exposure . Peripheral monocyte percentage . Saliva salivary agglutinin . Electronic waste Abbreviations Pb lead LnPb natural logarithmic transformation of blood Pb level SAG salivary agglutinin PM 2.5 fine particulate matter POPs persistent organic pollutants BMI body mass index AMP antimicrobial protein and peptide WBC white blood cell E-waste electronic waste CI confidence interval * Xijin Xu

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“…In saliva, the concentration of DMBT1 SAG is approximately 20 μg/ml (Sonesson et al 2011 ). DMBT1 plays various roles in innate immunity, e.g., by activating the MBL-mediated lectin pathway of the complement system (Gunput 2016 ); it binds to surfactant proteins A and D (Holmskov et al 1997 ; Tino and Wright 1999 ), IgA (Ligtenberg et al 2004 ), MUC5B (Thornton et al 2001 ), C-type lectin receptors DC-SIGN and Langerin (Boks et al 2016 ), influenza virus and HIV (Hartshorn et al 2003 ; Stoddard et al 2007 ), the dental hard tissue (Bikker et al 2013 ), and a wide spectrum of bacteria (Bikker et al 2004 ; Bikker et al 2002 ; Leito et al 2008 ; Madsen et al 2010 ). In particular, the SRCR/SID region in DMBT1 appears to play a dominant role in bacterial binding (Bikker et al 2004 ; Bikker et al 2002 ; Brittan and Nobbs 2015 ; Kukita et al 2013 ).…”

Section: Introductionmentioning

confidence: 99%

The scavenging capacity of DMBT1 is impaired by germline deletions

et al. 2017

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The Scavenger Receptor Cysteine-Rich (SRCR) proteins are an archaic group of proteins characterized by the presence of multiple SRCR domains. They are membrane-bound or secreted proteins, which are generally related to host defense systems in animals. Deleted in Malignant Brain Tumors 1 (DMBT1) is a SRCR protein which is secreted in mucosal fluids and involved in host defense by pathogen binding by its SRCR domains. Genetic polymorphism within DMBT1 leads to DMBT1-alleles giving rise to polypeptides with interindividually different numbers of SRCR domains, ranging from 8 SRCR domains (encoded by 6 kb DMBT1 variant) to 13 SRCR domains (encoded by the 8 kb DMBT1 variant). In the present study, we have investigated whether reduction from 13 to 8 amino-terminal SRCR domains leads to reduction of bacterial binding. The 6 kb variant bound ~20–45% less bacteria compared to the 8 kb variant. These results support the hypothesis that genetic variation in DMBT1 may influence microbial defense.

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The Human Glycoprotein Salivary Agglutinin Inhibits the Interaction of DC-SIGN and Langerin with Oral Micro-Organisms

Cited by 10 publications

References 46 publications

Salivary Trefoil Factor Family (TFF) Peptides and Their Roles in Oral and Esophageal Protection: Therapeutic Potential

Salivary Trefoil Factor Family (TFF) Peptides and Their Roles in Oral and Esophageal Protection: Therapeutic Potential

Oral antimicrobial activity weakened in children with electronic waste lead exposure

The scavenging capacity of DMBT1 is impaired by germline deletions

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