Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus

TLDR

Accumulation of apoptotic waste can serve as autoantigens that sustain autoimmune responses. The study aimed to determine whether impaired phagocyte function in SLE patients reduces apoptotic cell clearance. Apoptosis was identified by morphology and propidium iodide staining, and phagocytosis of autologous and heterologous apoptotic cells by cultured PBMCs and in vitro‑differentiated macrophages was assessed microscopically, including annexin V inhibition studies. SLE patients exhibit reduced, phagocyte‑dependent clearance of apoptotic cells, and annexin V inhibition reproduces this defect, suggesting that impaired noninflammatory engulfment may contribute to autoimmunity.

Abstract

Objective To investigate whether the established impaired phagocyte function in systemic lupus erythematosus (SLE) patients also affects apoptotic cell clearance. Accumulation of apoptotic waste as a source for autoantigens that induce and maintain autoimmune responses is discussed. Methods Apoptosis was detected by morphology and propidium iodide staining. In vitro phagocytosis of autologous apoptotic cells in cultured peripheral blood mononuclear cells was evaluated microscopically. Cross-feeding experiments were performed to investigate phagocytosis of heterologous apoptotic cells by in vitro-differentiated macrophages. Furthermore, the effect of annexin V on the phagocytosis of apoptotic cells was investigated. Results Reduced clearance of apoptotic cells in SLE patients was observed. The defective clearance appeared to reflect phagocyte dysfunction and not an abnormal execution of apoptosis. A similar picture was seen when in vitro-differentiated macrophages from control populations were treated with annexin V. Conclusion Noninflammatory engulfment phagocytosis of apoptotic cells is decreased in SLE patients. Persistently circulating apoptotic waste may encounter inflammatory removal pathways and serve as immunogen for the induction of autoreactive lymphocytes and as antigen for immune complex formation.