C-reactive protein functions as a negative regulator of macrophage activation induced by apoptotic DNA

C-reactive protein(CRP),an acute-phase protein with an ability to bind to nuclear antigen,has been reported to regulate cytokine secretion and modulate immune responses.We previously reported that activated syngeneic lymphocyte-derived apoptotic DNA(apopDNA)could induce macrophage activation and contribute to the initiation and progression of lupus nephritis.It is reasonable to hypothesize that CRP might regulate apopDNA-induced macrophage activation.Herein,CRP was shown to promote macrophage-mediated apopDNA uptake by binding to apopDNA(CRP/apopDNA complex).Notably,CRP/apopDNA treatment inhibited the production of inflammatory cytokines and chemokines by macrophages which could be induced by apopDNA alone.Further coculture and transwell studies revealed that CRP/apopDNA-induced macrophages prohibited apopDNA-induced macrophage activation in an IL-10 dependent manner.These results provide insight into the potential mechanism of CRP regulatory activity in macrophage activation induced by apopDNA in the context of lupus nephritis and other autoimmune diseases.