Bijl M, Reefman E, Horst G, Limburg P C, Kallenberg C G M
Department of Internal Medicine, Division of Clinical Immunology, University Hospital, The Netherlands.
Ann Rheum Dis. 2006 Jan;65(1):57-63. doi: 10.1136/ard.2005.035733. Epub 2005 May 26.
Defects in phagocytosis of apoptotic cells have a role in the pathogenesis of autoimmune diseases. Decrease of phagocytosis of apoptotic cells occurs in systemic lupus erythematosus (SLE). Factors underlying this decrease are, presently, unknown.
To analyse the expression of relevant membrane receptors of monocyte derived macrophages (MDM) from patients with SLE and assess their ability to phagocytose apoptotic cells in comparison with MDM from healthy controls. Additionally, to compare phagocytosis in the presence of SLE sera with that in normal human serum (NHS).
Human peripheral blood monocytes were isolated from patients and controls, and cultured for 7 days to obtain MDM. Membrane expression of CD14, CD18, CD36, and CD51/61 was measured. MDM were incubated with apoptotic Jurkat cells in the presence of NHS or serum from patients with active or inactive disease.
No differences in phagocytosis capacity were found between MDM from patients and controls. Membrane expression of the respective receptors was comparable in patients and controls. However, when MDM from controls were incubated with apoptotic cells in patient serum, phagocytosis was significantly decreased in comparison with incubation in NHS. This effect depended on the patients' disease activity and could be reversed by addition of NHS. Reduced uptake of apoptotic cells was associated with decreased levels of complement C1q, C4, and C3, but not with levels of complement factor B.
Reduced uptake of apoptotic cells by MDM from patients with SLE is not an intrinsic defect but is serum dependent and associated with decreased levels of C1q, C4, and C3.
凋亡细胞吞噬缺陷在自身免疫性疾病的发病机制中起作用。系统性红斑狼疮（SLE）患者中凋亡细胞的吞噬作用降低。目前，这种降低的潜在因素尚不清楚。
分析SLE患者单核细胞衍生巨噬细胞（MDM）相关膜受体的表达，并与健康对照者的MDM相比，评估其吞噬凋亡细胞的能力。此外，比较SLE血清存在时与正常人血清（NHS）存在时的吞噬作用。
从患者和对照者中分离人外周血单核细胞，培养7天以获得MDM。检测CD14、CD18、CD36和CD51/61的膜表达。在NHS或活动期或非活动期疾病患者的血清存在下，将MDM与凋亡的Jurkat细胞一起孵育。
患者和对照者的MDM在吞噬能力上未发现差异。患者和对照者各自受体的膜表达相当。然而，当对照者的MDM与患者血清中的凋亡细胞一起孵育时，与在NHS中孵育相比，吞噬作用显著降低。这种效应取决于患者的疾病活动度，并且可以通过添加NHS来逆转。凋亡细胞摄取减少与补体C1q、C4和C3水平降低有关，但与补体因子B水平无关。
SLE患者的MDM对凋亡细胞摄取减少不是内在缺陷，而是血清依赖性的，并且与C1q、C4和C3水平降低有关。
