Papel do receptor de quimiocina CCR2 sobre os eventos vasculares e celulares da resposta inflamatória na interação implante/hospedeiro em camundongos

Abstract

Host and synthetic implants interactions may induce an inflammatory response so called “foreign body” reaction that could be modulated by a range of inflammatory mediators such as Chemokine Receptor 2 (CCR2). In this study, using mice with gene deletion of CCR2 we analysed the role of this receptor on cellular, inflammatory and vascular events during the host/implant interactions in mice. The kinetics of vascular, inflammatory and fibrogenic alterations in polyether-polyurethane discs removed at 1, 4, 7 and 14 days postimplantation in wild type (WT) and knockout (KO) mice was evaluated. It was observed a lower blood flow in both skin and KO implants. Haemoglobin content (vascular index) was lower in implants from KO mice compared with that from wild type counterparts. Neutrophils accumulation was higher in KO implants, but macrophages accumulation was apparently decreased in these implants. CCL2 levels were higher in KO implants, but TGF-β1, collagen deposition and giant cells number were lower in KO implants compared to WT implants. Immunophenotyping evaluated by flow cytometry revealed that both, implants and peripheral blood from WT and KO mice expressed characteristic cell surface markers of stem and progenitor cells. In addition, CCR2 deletion led to increased expression of these markers in cells of peripheral blood from KO mice. The experimental system used in this study has contributed to a better understanding of the CCR2 role on vascular, inflammatory, fibrogenic events and cell surface markers expression during implant/host interactions in mice.