IMPAIRED PHAGOCYTOSIS OF APOPTOTIC CELL MATERIAL BY MONOCYTE-DERIVED MACROPHAGES FROM PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS

Objective. To investigate whether the established impaired phagocyte f unction in systemic lupus erythematosus (SLE) patients also affects ap optotic cell clearance. Accumulation of apoptotic waste as a source fo r autoantigens that induce and maintain autoimmune responses is discus sed. Methods. Apoptosis was detected by morphology and propidium iodid e staining. In vitro phagocytosis of autologous apoptotic cells in cul tured peripheral blood mononuclear cells was evaluated microscopically . Cross-feeding experiments were performed to investigate phagocytosis of heterologous apoptotic cells by in vitro-differentiated macrophage s. Furthermore, the effect of annexin V on the phagocytosis of apoptot ic cells was investigated. Results. Reduced clearance of apoptotic cel ls in SLE patients was observed. The defective clearance appeared to r eflect phagocyte dysfunction and not an abnormal execution of apoptosi s. A similar picture was seen when in vitro-differentiated macrophages from control populations were treated with annexin V. Conclusion. Non inflammatory engulfment phagocytosis of apoptotic cells is decreased i n SLE patients. Persistently circulating apoptotic waste may encounter inflammatory removal pathways and serve as immunogen for the inductio n of autoreactive lymphocytes and as antigen for immune complex format ion.