Tas S W, Quartier P, Botto M, Fossati-Jimack L
Rheumatology Section, Division of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, Du Cane Road, London W12 0NN, UK.
Ann Rheum Dis. 2006 Feb;65(2):216-21. doi: 10.1136/ard.2005.037143. Epub 2005 Jul 13.
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.
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.
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.
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.
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.
有研究表明,巨噬细胞对凋亡细胞处理存在缺陷在系统性红斑狼疮(SLE)的发病机制中起关键作用。内在缺陷和血清因子的相对作用仍存在争议。
比较SLE患者、类风湿关节炎患者及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。
将健康供者或SLE或类风湿关节炎患者外周血来源的单核细胞诱导分化为巨噬细胞。通过流式细胞术检测巨噬细胞对凋亡细胞的体外摄取,以区分结合和内化情况。
与健康供者相比,SLE和类风湿患者的单核细胞在贴壁方面存在明显缺陷。血清缺失或热灭活导致巨噬细胞对凋亡细胞的结合和吞噬减少。与正常对照相比,类风湿和SLE患者的巨噬细胞表面结合凋亡细胞的百分比相似。然而,即使在正常人血清存在的情况下,SLE患者的巨噬细胞在凋亡细胞内化方面与健康对照相比仍存在显著缺陷。
SLE和类风湿关节炎患者的单核细胞在贴壁能力上存在类似缺陷。然而,只有SLE患者的巨噬细胞表现出吞噬凋亡细胞的能力受损,这表明内在细胞缺陷可能是导致这一现象的原因。