CCR5 Mediates Pro-osteoclastic and Osteoclastogenic Leukocyte Chemoattraction

Author(s)

Ferreira, Jr., S. B. ^[1] ; Repeke, C. E. ^[1] ; Raimundo, F. M. ^[1] ; Nunes, I. S. ^[1] ; Avila-Campos, M. J. ^[2] ; Ferreira, B. R. ^[3] ; Santana da Silva, J. ^[3] ; Campanelli, A. P. ^[1] ; Garlet, G. P. ^[1]

Affiliation

^[1] Univ Sao Paulo, FOB USP, Sch Dent Bauru, Dept Biol Sci, OSTEOimmunol Lab, BR-17012901 Bauru, SP - Brazil

^[2] Univ Sao Paulo, ICB USP, Inst Biomed Sci, Dept Microbiol, BR-17012901 Bauru, SP - Brazil

^[3] Univ Sao Paulo, FMRP USP, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-17012901 Bauru, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF DENTAL RESEARCH; v. 90, n. 5, p. 632-637, MAY 2011.
• Web of Science Citations: 18

Abstract

Periodontal disease (PD) progression involves the selective leukocyte infiltration into periodontium, supposedly mediated by the chemokine/chemokine receptor system. In this study, we investigated the role of chemokine receptor CCR5 in the immunoregulation of experimental PD in C57BL/6 (WT) and CCR5KO mice. Aggregatibacter actinomycetem comitans infection triggered the chemoattraction of distinct CCR5+ leukocyte subpopulations (determined by flow cytometry): CCR5+F4/80+ leukocytes, which co-express CD14, CCR2, TNF-alpha, and IL-1 beta, indicative of activated macrophages; and CCR5+CD4+ cells, which co-express CXCR3, IFN-gamma, and RANKL, indicative of Th1 lymphocytes, therefore comprising pro-osteoclastic and osteoclastogenic cell subsets, respectively. CCR5KO mice presented a lower PD severity (lower inflammation and alveolar bone loss) when compared with the WT strain, since the migration of F4/80+, TNF-alpha+, CD4+, and RANKL+ cells specifically decreased due to the lack of CCR5. Also, ELISA analysis demonstrated that the production of TNF-alpha, IL-1 beta, IL-6, IFN-gamma, and RANKL in periodontal tissues was significantly decreased in the CCR5KO strain. The periodontal bacterial load and antimicrobial patterns were unaltered in CCR5KO mice. Our results demonstrate that the chemokine receptor is involved in the migration of distinct leukocyte subpopulations throughout experimental PD, being a potential target for therapeutic intervention in PD. (AU)

• FAPESP's process: 06/04949-1 - Modulation of osteoclastogenic factors expression and their inhibitors by CCR5+ cells in experimental periodontal disease
• Grantee: Francine Mariana Raimundo
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 08/11174-1 - KINETICS OF OSTEOCLAST CO-STIMULATORY MOLECULES THROUGHOUT EXPERIMENTAL PERIODONTITIS AND MICE AND ITS MODULATION BY CYTOKINES
• Grantee: Carlos Eduardo Palanch Repeke
• Support Opportunities: Scholarships in Brazil - Doctorate