Uptake of apoptotic leukocytes by synovial lining macrophages inhibits immune complex-mediated arthritis

Previously we have shown that synovial lining macrophages (SLMs) determine the onset of experimental immune complex-mediated arthritis (ICA). During j oint inflammation, many leukocytes undergo apoptosis, and removal of leukoc ytes by SLMs may regulate resolution of inflammation. In this study we inve stigated binding and uptake of apoptotic leukocytes by SLMs and its impact on the onset of murine experimental arthritis. We used an in vitro model to evaluate phagocytosis of apoptotic cells on chemotaxis. Phagocytosis of ap optotic thymocytes resulted in a significant decrease (58%) of chemotactic activity for polymorphonuclear neutrophils (PMNs). If apoptotic cells were injected directly into a normal murine knee joint, SLMs resulted in a promi nent uptake of cells. After ICA induction, electron micrographs showed that apoptotic leukocytes were evidently present in SLMs on days 1 and 2. Injec tion of apoptotic leukocytes into the knee joint 1 h before induction of IC A significantly inhibited PMN infiltration into the knee joint at 24 h (61% decrease). This study indicates that uptake of apoptotic leukocytes by SLM reduces chemotactic activity and inhibits the onset of experimental arthri tis. These findings indicate an important mechanism in the resolution of jo int inflammation.