DENDRITIC CELL AND CORONARY VASCULAR SMOOTH MUSCLE CELL INTERACTIONS

BACKGROUND: Vascular remodeling is a chronic multi-factorial disease in which systemic or local inflammatory pathogenetic mechanisms play a key role . It has been become evident that the dendritic cells (DCs), antigen presenting cells, are also involved in driving the chronic vascular inflammation which characterizes this disease . DCs are present in the vascular wall as vascular-associated lymphoid tissue and their number increases during atherosclerosis. Despite the well-known role of inflammatory and immunological mechanisms involved in the various stages of the atherogenic process, the pathogenetic and immunomodulant role of vascular DCs in the activation of vascular smooth muscle cells (VSMCs) is still unclear. Since no informations are still available on the role of DCs on the activation of these cells, the aim of the study was investigate the interaction between DCs and VSMCs. METHODS: DC were generated from peripheral blood of healthy donors by trans-differentiation of monocytes CD14+. Mature DCs expressed high levels of co-stimulatory molecules CD80, CD86, the maturation marker CD83 and HLA-DR. In order to investigate the possible effects of VSMC on DC maturation, a co-culture model between coronary smooth muscle cells (CASMC) and immature DCs was set up. CASMCs, pretreated and not pretreated with inflammatory cytokines, stimulated DC maturation as demonstrated by flow cytometry analysis of DC markers and by functional assay as mixed lymphocyte reaction. We then studied the adhesion property of mature DCs on CASMC pretreated with inflammatory cytokines. RESULTS: Mature DCs were able to adhere to human CASMCs while immature DCs did not. The pretreatment of CASMCs with inflammatory cytokines stimulated ICAM-1 and VCAM-1 mRNA expression and increased DC adhesion. This DC adhesion was impaired by CD18 and CD11c neutralizing antibodies, thus confirming the involvement of vascular adhesion molecules. CONCLUSIONS: These findings suggest that the inflammatory environment may stimulate the interaction between DCs and VSMCs thus driving vascular remodeling.