In vivo role of CCR2 and CCR5 receptors in the imune and inflammatory response after a classic biomaterial (Ti) grafting

• Grant number: 12/50575-7
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2013
• End date: May 31, 2015
• Field of knowledge: Health Sciences - Dentistry
• Agreement: CNPq - First Projects Program
• Principal Investigator: Gustavo Pompermaier Garlet
• Grantee: Gustavo Pompermaier Garlet
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil

Abstract

Studies have shown that the nature (transient or chronic) and the magnitude of the inflammatory and immunological response, generated by a biomaterial, may be decisive in the implant success or failure. Macrophages play a critical role in host response to a biomaterial grafting, and in this context, the chemokines receptors CCR2 and CCR5 play a critical role in this response, since macrophage migration to response sites depends on such receptors. Indeed recently, it has demonstrated a regulatory monocyte/macrophage role and/or their products on osteogenic response associated to titanium-based biomaterial and such response depends on the macrophage activation. Thus, our hypothesis is that CCR2 and CCR5 receptores mediate the migration of macrophages after a classic biomaterial (Ti) grafting, which is followed by macrophage activation via DAMPs is responsible and them for developing a transient inflammatory response of low magnitude, which in turn contributes to the subsequent process of osteogenesis at the interface between bone and biomaterial. To unravel the role of CCR2 and CCR5 receptors in the host inflammatory immune response after biomaterial grafting, we will analyze in a comparative way the response of C57BL/6 (WT), CCR2KO and CCR5KO mice to the grafting of Ti discs into subcutaneous and intraperitenal environments, using histologic, histomorphometric, molecular (RealTimePCR & PCR-Array) and immunoenzimatic (ELISarray) as investigation tools. (AU)