Oral Mucosal Lamina Propria-Progenitor Cells Exert Antibacterial Properties via the Secretion of Osteoprotegerin and Haptoglobin

摘要

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. SignificanceOral 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.