Involvement of phosphatidylserine, αvβ3, CD14, CD36, and complement C1q in the phagocytosis of primary necrotic lymphocytes by macrophages

被引:76
作者
Böttcher, A
Gaipl, US
Fürnrohr, BG
Herrmann, M
Girkontaite, I
Kalden, JR
Voll, RE
机构
[1] Nikolaus Fiebiger Ctr Mol Med, IZKF Res Grp N2, D-91054 Erlangen, Germany
[2] Univ Erlangen Nurnberg, Erlangen, Germany
来源
ARTHRITIS AND RHEUMATISM | 2006年 / 54卷 / 03期
关键词
D O I
10.1002/art.21660
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. Uningested dead cells may be an important source of autoantigens and may trigger autoimmune diseases such as systemic lupus erythematosus (SLE). Multiple receptors involved in the clearance of apoptotic cells have been described; however, little is known about the receptors and ligands involved in uptake of necrotic cells that release autoantigens as well. Methods. The uptake of autologous necrotic peripheral blood lymphocytes into human monocyte-derived macrophages was qualitatively and quantitatively monitored by confocal microscopy and 2-color flow cytometry, respectively. Blocking experiments were performed to examine the receptors and molecules involved in the phagocytosis of necrotic cells. Cytokine secretion by lipopolysaccharide-activated monocytes and macrophages was determined by enzyme-linked immunosorbent assay. Results. Phosphatidylserine, which was exposed on necrotic as well as apoptotic cells, promoted the recognition and removal of, primary necrotic lymphocytes. Several macrophage receptor systems, including the thrombospondin-CD36-alpha v beta 3 complex, CD14, and the complement component C1q, contributed to the engulfment of necrotic cells. Necrotic peripheral blood lymphocytes slightly increased the lipopolysaccharide-induced secretion of interleukin-10 and reduced the secretion of tumor necrosis factor a in monocytes and macrophages. Conclusion. Our results indicate that at least some of the receptors and adaptors mediating the uptake of apoptotic cells are also involved in the clearance of necrotic cells. Hence, necrotic cells engage phagocyte receptors such as CD36, which mediate antiinflammatory signals from apoptotic cells. Necrotic cells consequently also have the potency to provide antiinflammatory signals to phagocytes; however, these signals may be overridden by proinflammatory factors released during necrosis. These findings have implications regarding the etiopathogenesis of autoimmune diseases such as SLE, in which impaired clearance of dead cells may foster autoimmunity by the release of potential autoantigens.
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页码:927 / 938
页数:12
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