title: Macrophage depletion abates Porphyromonas gingivalis-induced alveolar bone resorption in mice.
abstract: The role of the macrophage in the immunopathology of periodontitis has not been well defined. In this study, we show that intraoral inoculation of mice with Porphyromonas gingivalis resulted in infection, alveolar bone resorption, and a significant increase in F4/80(+) macrophages in gingival and submandibular lymph node tissues. Macrophage depletion using clodronate-liposomes resulted in a significant reduction in F4/80(+) macrophage infiltration of gingival and submandibular lymph node tissues and significantly (p < 0.01) less P. gingivalis-induced bone resorption compared with controls in BALB/c and C57BL/6 mice. In both mouse strains, the P. gingivalis-specific IgG Ab subclass and serum cytokine [IL-4, IL-10, IFN-γ, and IL-12 (p70)] responses were significantly (p < 0.01) lower in the macrophage-depleted groups. Macrophage depletion resulted in a significant reduction in the level of P. gingivalis infection, and the level of P. gingivalis infection was significantly correlated with the level of alveolar bone resorption. M1 macrophages (CD86(+)), rather than M2 macrophages (CD206(+)), were the dominant macrophage phenotype of the gingival infiltrate in response to P. gingivalis infection. P. gingivalis induced a significant (p < 0.01) increase in NO production and a small increase in urea concentration, as well as a significant increase in the secretion of IL-1β, IL-6, IL-10, IL-12 (p70), eotaxin, G-CSF, GM-CSF, macrophage chemoattractant protein-1, macrophage inflammatory protein-α and -β, and TNF-α in isolated murine macrophages. In conclusion, P. gingivalis infection induced infiltration of functional/inflammatory M1 macrophages into gingival tissue and alveolar bone resorption. Macrophage depletion reduced P. gingivalis infection and alveolar bone resorption by modulating the host immune response.
authors: Oral Health Cooperative Research Centre, Melbourne Dental School, The University of Melbourne, Melbourne, Victoria 3010, Australia; and.
authors: Roselind S
authors: RS
authors: Lam
authors: Oral Health Cooperative Research Centre, Melbourne Dental School, The University of Melbourne, Melbourne, Victoria 3010, Australia; and.
authors: Neil M
authors: NM
authors: O'Brien-Simpson
authors: Oral Health Cooperative Research Centre, Melbourne Dental School, The University of Melbourne, Melbourne, Victoria 3010, Australia; and.
authors: Jason C
authors: JC
authors: Lenzo
authors: Oral Health Cooperative Research Centre, Melbourne Dental School, The University of Melbourne, Melbourne, Victoria 3010, Australia; and.
authors: James A
authors: JA
authors: Holden
authors: Oral Health Cooperative Research Centre, Melbourne Dental School, The University of Melbourne, Melbourne, Victoria 3010, Australia; and.
authors: Gail C
authors: GC
authors: Brammar
authors: Oral Health Cooperative Research Centre, Melbourne Dental School, The University of Melbourne, Melbourne, Victoria 3010, Australia; and.
authors: Katrina A
authors: KA
authors: Walsh
authors: Oral Health Cooperative Research Centre, Melbourne Dental School, The University of Melbourne, Melbourne, Victoria 3010, Australia; and.
authors: Judith E
authors: JE
authors: McNaughtan
authors: Oral Health Cooperative Research Centre, Melbourne Dental School, The University of Melbourne, Melbourne, Victoria 3010, Australia; and.
authors: Dennis K
authors: DK
authors: Rowler
authors: Department of Molecular Cell Biology, Faculty of Medicine, Vrije Universiteit Medical Center, 1081 BT Amsterdam, the Netherlands.
authors: Nico
authors: N
authors: Van Rooijen
authors: Oral Health Cooperative Research Centre, Melbourne Dental School, The University of Melbourne, Melbourne, Victoria 3010, Australia; and e.reynolds@unimelb.edu.au.
authors: Eric C
authors: EC
authors: Reynolds
mesh_terms: D016301:Alveolar Bone Loss / Q000276:immunology* / Q000473:pathology; D000818:Animals; D016866:Bacteroidaceae Infections / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010518:Periodontitis / Q000276:immunology* / Q000473:pathology; D016966:Porphyromonas gingivalis / Q000276:immunology*
chemical_list: D016207:Cytokines