Human C-Reactive Protein Activates Monocyte-Derived Dendritic Cells and Induces Dendritic Cell-Mediated T-Cell Activation

Abstract

Objective-Recent studies proposed a pathogenic role for C-reactive protein (CRP), an independent predictor of cardiovascular disease (CVD), in atherosclerosis. Therefore, we tested whether CRP may modulate dendritic cell (DC) function, because these professional antigen-presenting cells have been implicated in atherogenesis. Methods and Results-Human monocyte-derived immature DCs were cultured with human CRP (0 to 60 g/mL) for 24 hours. Thereafter, activation markers were measured by flow-cytometry and DCs were cocultured with CFSE-labeled lymphocytes to measure T-cell proliferation and interferon (IFN)-␥ secretion after 8 days.

Different Distribution of Pentraxin 3 and C-Reactive Protein in Coronary Atherosclerotic Plaques

“…Furthermore, recent vitro studies indicated that T-lymphocytes incubated with CRP-pulsed dendritic cells displayed increased IFN-γ secretion and proliferation 34) and that CRP polarized human monocyte differentiation toward M1 macrophages and also prevented the polarization of IL-4 induced M2 macrophage phenotypes 35) . These results might support our findings that, in atherectomy specimens, CRP but not PTX3 is significantly correlated with T-lymphocytes and also, the CRP-rich area in post-mortem coronary plaques could be characterized by the magnitude of CD163-negative macrophages.…”

Danhong Inhibits Oxidized Low-Density Lipoprotein&ndash;Induced Immune Maturation of Dentritic Cells via a Peroxisome Proliferator Activated Receptor <I>&gamma;</I>&ndash;Mediated Pathway

“…DCs present in normal arteries are immature and become mature during atherogenesis, and emergence of dendritic cells in rupture-prone regions of vulnerable carotid plaques was documented (7). Proatherogenic factors such as oxidized low-density lipoproteins (ox-LDL) (8,9), advanced glycation end products (10), and C-reactive protein (CRP) (11) were reported to induce DC maturation and subsequently resulting in T-lymphocyte activation. Therefore, an agent able to inhibit the function of DCs may be beneficial in the treatment of atherosclerotic disease (12).…”

Regulated conformation changes in C-reactive protein orchestrate its role in atherogenesis

“…Knock-in of human CRP in rabbits, on the other hand, appeared to reduce the lesion formation, albeit with no statistical significance [35]. Even worse is that in vitro studies frequently generate conflicting results [36][37][38][39][40][41][42][43][44][45] and some of the reported activities of CRP have been ascribed to impurities such as azide or endotoxin [39,46,47]. The acute-phase reactant nature of CRP adds an additional layer of complexity: how does a protein with two to three orders of dynamic fluctuation in its plasma levels function as a fine modulator of sophisticated cellular or physiological systems [1]?…”

“…Moreover, disruption of lipid rafts by MβCD or nystatin eliminated the stimulation effects of Cysmutated mCRP on EC and in rabbit vessels. Accordingly, we identified a cholesterol binding motif (CBM; a.a. [35][36][37][38][39][40][41][42][43][44][45][46][47] containing Cys36 in the sequence of human CRP which has been conserved throughout evolution. Indeed, reduction or mutating cysteines promoted the interactions of Cysmutated or reduced mCRP with both model and cell membranes.…”