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Division of Rheumatology, University Medical Centre Nijmegen, the Netherlands,
* Division of Nephrology, University Medical Centre Nijmegen, the Netherlands,
Division of Pathology, University Medical Centre Nijmegen, the Netherlands
Correspondence: P.L.E.M. van Lent, Division of Rheumatology, University Medical Center Nijmegen, Geert Grooteplein 26-28, 6500 HB Nijmegen, the Netherlands. E-mail: p.vanlent{at}reuma.azn.nl.
Previously we have shown that synovial lining macrophages (SLMs) determine the onset of experimental immune complexmediated arthritis (ICA). During joint inflammation, many leukocytes undergo apoptosis, and removal of leukocytes by SLMs may regulate resolution of inflammation. In this study we investigated 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 apoptotic 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 prominent uptake of cells. After ICA induction, electron micrographs showed that apoptotic leukocytes were evidently present in SLMs on days 1 and 2. Injection of apoptotic leukocytes into the knee joint 1 h before induction of ICA 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 arthritis. These findings indicate an important mechanism in the resolution of joint inflammation.
Key Words: joint inflammation immune complexes synovium apoptotic cells synovial lining macrophages chemotaxis
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