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-beta1-6-glucotriosyl-beta1-3-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 x 10 (6), 4 x 10 (7), and 4 x 10 (8) colony-forming units (CFU). In the second set of experiments the chambers were inoculated with 5 x 10 (8) 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.
Niederman
Richard
R
The Forsyth Institute, 140 Fenway, Boston, MA 02115, USA.
Kelderman
Hans
H
Socransky
Sigmund
S
Ostroff
Gary
G
Genco
Caroline
C
Kent
Ralph
R
Stashenko
Philip
P
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001424:Bacterial Infections / Q000188:drug therapy* / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005891:Gingivitis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D005936:Glucans / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D020556:Neutrophil Infiltration / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D016966:Porphyromonas gingivalis / Q000187:drug effects*; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors; D047071:beta-Glucans
D000276:Adjuvants, Immunologic; D005936:Glucans; D047071:beta-Glucans; C069894:poly-1-6-glucopyranosyl-1-3-glucopyranose glucan