The uptake and degradation of DNA is impaired in macrophages and dendritic cells from NZB/W F(1) mice

Abstract

DNA/anti-DNA Ab immune complexes seem to play the critical roles in the development of systemic lupus erythematosus (SLE). However, little is known about the removal of DNA by MPhi and DC. We found that elicited peritoneal MPhis and BM-derived DCs from a lupus-prone strain of New Zealand Black/White F(1) (NZB/W) mice showed impaired DNA uptake and degradation compared with those from control ICR mice. The impairment was mainly observed as the reduced degradation of DNA probably in endosomal compartment and this impaired DNA degradation might, at least in part, result from the reduced DNA uptake in these phagocytic cells. In addition, these impairments was not related to the disease progression since the cells from diseased, 6-month-old NZB/W mice as well as the cells from prediseased, 5-week-old NZB/W mice also exhibited the similar impairment. We also found that the MPhis and DCs of diseased NZB/W mice showed reduced DNA binding at 4 degrees C. However, this reduced DNA binding could be restored to the control level by pretreatment with DNase. Interestingly, this pretreatment had little effect on the DNA uptake in MPhis and DCs of diseased NZB/W mice at 37 degrees C. Hence, the present results imply an impaired function of lupus MPhis and DCs of NZB/W mice to cause retained DNA clearance.