title: Oral Mucosal Lamina Propria-Progenitor Cells Exert Antibacterial Properties via the Secretion of Osteoprotegerin and Haptoglobin.
abstract: The oral cavity possesses a diverse microflora, yet recurrent infections within healthy individuals are rare. Wound healing within the buccal mucosa is preferential, potentially because of the presence of oral mucosal lamina propria-progenitor cells (OMLP-PCs). In addition to their multipotency, OMLP-PCs demonstrate potent immunosuppressive properties. The present study investigated whether OMLP-PCs possess antibacterial properties, directly interacting with microorganisms and contributing to the maintenance of a balanced oral microflora. Gram-positive and -negative bacteria were cocultured with OMLP-PCs, buccal mucosal fibroblasts, or their respective conditioned media (CM). Bacterial growth was significantly inhibited when cocultured with OMLP-PCs or their CM. No antibacterial activity was apparent within the fibroblasts. Analysis of the OMLP-PC CM indicated constitutive secretion of osteoprotegerin (OPG) and haptoglobin (Hp). Exposure of the bacteria to OPG or Hp demonstrated their differential antibacterial properties, with neutralization/blocking studies confirming that the growth of Gram-positive bacteria was partially restored by neutralizing OPG within OMLP-PC CM; blocking Hp restored the growth of Gram-negative bacteria. The present study demonstrates, for the first time, the broad-spectrum antibacterial properties of OMLP-PCs. We report the direct and constitutive antibacterial nature of OMLP-PCs, with retention of this effect within the CM suggesting a role for soluble factors such as OPG and Hp. Knowledge of the immunomodulatory and antibacterial properties of these cells could potentially be exploited in the development of novel cell- or soluble factor-based therapeutics for the treatment of infectious diseases such as pneumonia or ailments such as chronic nonhealing wounds.
  
  
  CONCLUSIONS
  Oral mucosal lamina propria-progenitor cells (OMLP-PCs) are a cell source with known immunomodulatory properties. The present report demonstrates the novel finding that OMLP-PCs possess potent antibacterial properties, halting the growth of Gram-positive and -negative bacteria through the secretion of soluble factors. OMLP-PCs constitutively secrete osteoprotegerin (OPG) and haptoglobin (Hp) at levels high enough to exert antibacterial action. OPG, a glycoprotein not previously known to be antibacterial, can suppress Gram-positive bacterial growth. Hp is only active against Gram-negative microorganisms. These findings indicate that OMLP-PCs could offer great potential in the development of novel cell- or soluble factor-based therapies for the treatment of infectious illness, such as bacterial pneumonia, through systemic infusion and of chronic wounds through local administration.
authors.affiliation: Wound Biology Group, Tissue Engineering and Reparative Dentistry, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom Cardiff Institute of Tissue Engineering and Repair, Cardiff University, Cardiff, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: Board-Davies
authors.affiliation: Wound Biology Group, Tissue Engineering and Reparative Dentistry, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom Cardiff Institute of Tissue Engineering and Repair, Cardiff University, Cardiff, United Kingdom.
authors.forename: Rachael
authors.initials: R
authors.lastname: Moses
authors.affiliation: Wound Biology Group, Tissue Engineering and Reparative Dentistry, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom Cardiff Institute of Tissue Engineering and Repair, Cardiff University, Cardiff, United Kingdom.
authors.forename: Alastair
authors.initials: A
authors.lastname: Sloan
authors.affiliation: Wound Biology Group, Tissue Engineering and Reparative Dentistry, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom Cardiff Institute of Tissue Engineering and Repair, Cardiff University, Cardiff, United Kingdom.
authors.forename: Phil
authors.initials: P
authors.lastname: Stephens
authors.affiliation: Wound Biology Group, Tissue Engineering and Reparative Dentistry, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom Cardiff Institute of Tissue Engineering and Repair, Cardiff University, Cardiff, United Kingdom Centre for Hematology and Regenerative Medicine, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden Lindsay.davies@ki.se.
authors.forename: Lindsay C
authors.initials: LC
authors.lastname: Davies
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001419:Bacteria / Q000254:growth & development*; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006242:Haptoglobins / Q000378:metabolism*; D006801:Humans; D008297:Male; D009061:Mouth Mucosa / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D053244:Osteoprotegerin / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D006242:Haptoglobins; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human
keywords: Antibacterial agents; Haptoglobin; Oral mucosa; Osteoprotegerin; Progenitor cell