Enhanced neutrophil emigration and Porphyromonas gingivalis reduction following PGG-glucan treatment of mice

Periodontal disease is the consequence of a mixed Gram-negative infection in the gingival sulcus and has been associated with deficits in the neutrophil response. A novel, and heretofore untested, alternative approach to therapy is the use of biological-response modulators that enhance the neutrophil response. Poly-β1-6-glucotriosyl-β1-3-glucopyranose glucan (PGG-glucan) is an immunomodulator, derived from yeast, which specifically enhances neutrophil priming, phagocytosis and bacterial killing while failing to induce inflammatory cytokine expression. The hypothesis tested was that PGG-glucan could enhance host resistance to a Gram-negative periodontal pathogen, Porphyromonas gingivalis. Chambers were implanted subcutaneously in the dorsolumbar region of C57BL/6J mice and allowed to heal for 14 days. PGG-glucan was administered subcutaneously to one-half of the animals and saline to the other half. In the first set of experiments the chambers were inoculated with P. gingivalis (A7436) at 4 × 10⁶, 4 × 10⁷, and 4 × 10⁸ colony-forming units (CFU). In the second set of experiments the chambers were inoculated with 5 × 10⁸ CFU of either P. gingivalis or Streptococcus sanguis, a Gram-positive oral microbe that is not periodontopathic. Chambers were sampled over the following 2 weeks. The results demonstrated that: (1) bacterial CFU and neutrophils increased with increasing bacterial inoculum (P < 0.02); (2) bacterial CFU were lower in the PGG-glucan-treated animals than in the saline controls (P < 0.02); and (3) neutrophil counts were higher in the PGG-glucan-treated animals than in the saline controls (P < 0.01). These results indicate that PGG-glucan significantly enhances neutrophil emigration and bacterial killing, thus decreasing the bacterial infection in this model system.