Macrophages from patients with SLE and rheumatoid arthritis have defective adhesion in vitro, while only SLE macrophages have impaired uptake of apoptotic cells
Macrophages from patients with SLE and rheumatoid arthritis have defective adhesion in vitro, while only SLE macrophages have impaired uptake of apoptotic cells
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DOI：
10.1136/ard.2005.037143
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发表时间：
2006-02-01
影响因子：
27.4
通讯作者：
Fossati-Jimack, L
中科院分区：
文献类型：
--
作者：
Tas, SW;Quartier, P;Fossati-Jimack, L
背景：有研究表明，巨噬细胞对凋亡细胞处理缺陷在系统性红斑狼疮（SLE）的发病过程中起关键作用。内在缺陷和血清因子的相对作用仍存在争议。
目的：比较系统性红斑狼疮患者、类风湿关节炎患者和健康对照者的单核细胞在体外分化为巨噬细胞以及结合/吞噬凋亡细胞的能力。
方法：取健康供者或系统性红斑狼疮患者及类风湿关节炎患者外周血来源的单核细胞，使其分化为巨噬细胞。通过流式细胞术检测巨噬细胞对凋亡细胞的体外摄取情况，该方法可区分结合与内化。
结果：与健康供者相比，系统性红斑狼疮和类风湿关节炎患者的单核细胞在塑料表面的黏附能力存在显著缺陷。血清缺失或热灭活会导致巨噬细胞对凋亡细胞的结合和吞噬减少。类风湿关节炎和系统性红斑狼疮患者的巨噬细胞与正常对照相比，其表面结合的凋亡细胞百分比相似。然而，即使存在正常人血清，系统性红斑狼疮患者的巨噬细胞与健康对照相比，在凋亡细胞内化方面仍存在显著缺陷。
结论：系统性红斑狼疮和类风湿关节炎患者的单核细胞在黏附塑料的能力上存在相似缺陷。然而，只有系统性红斑狼疮患者的巨噬细胞在吞噬凋亡细胞的能力上受损，这表明一种内在的细胞缺陷可能是这种现象的原因。
Background: It has been suggested that defective handling of apoptotic cells by macrophages plays a key role in the development of systemic lupus erythematosus (SLE). The relative contribution of intrinsic defects and serum factors remains controversial.Objective: To compare monocytes from SLE patients, patients with rheumatoid arthritis, and healthy controls for their ability to differentiate in vitro into macrophages and to bind/engulf apoptotic cells.Methods: Peripheral blood derived monocytes from healthy donors or from patients with SLE or rheumatoid arthritis were allowed to differentiate into macrophages. The in vitro uptake of apoptotic cells by macrophages was evaluated by a flow cytometry assay that allowed discrimination between binding and internalisation.Results: Monocytes from SLE and rheumatoid patients showed a striking defect in adherence to plastic compared with healthy donors. Absence or heat inactivation of serum resulted in a reduction in the binding and engulfment of apoptotic cells by macrophages. Macrophages from rheumatoid and SLE patients had similar percentages of apoptotic cells bound to their surface compared with normal controls. However, macrophages from SLE patients showed a significant defect in the internalisation of apoptotic cells compared with those from healthy controls, even in the presence of normal human serum.Conclusions: Monocytes from patients with SLE and rheumatoid arthritis have a similar defect in their capacity to adhere to plastic. However, only macrophages from SLE patients showed an impaired ability to engulf apoptotic cells, which indicates that an intrinsic cellular defect may be responsible for this phenomenon.