Department for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Bavaria, 91054, Germany.
Autoimmunity. 2010 Apr;43(3):232-5. doi: 10.3109/08916930903510930.
Deficiencies in the recognition and engulfment of apoptotic cells have been reported in patients with systemic lupus erythematosus (SLE). If dying cells are not promptly cleared, they undergo secondary necrosis and release nuclear autoantigens. Secondarily necrotic cell-derived material (SNEC) can be generated in vitro employing various methods. SNEC generated by either methods shows similar DNA content, light scatter characteristics, and binding pattern of dead and dying cell ligands and is readily recognized by autoantibodies (AAb) of many patients with SLE. In whole blood, AAb opsonize SNEC and foster its uptake by blood-borne non-professional phagocytes. We observed a significant secretion of the inflammatory cytokines IL-8 and TNF-alpha by phagocytes which had engulfed different types of opsonized SNEC. Phagocytosis of SNEC and the subsequent production of inflammatory cytokines were strongly influenced by the presence of DNA in this prey, since DNase I treatment reduced both the uptake of SNEC and the induction of IL-8 and TNF-alpha production. In conclusion, the proinflammatory phagocytosis by circulating phagocytes of IgG-opsonized cellular remnants fosters systemic inflammation in SLE.
已报道系统性红斑狼疮（SLE）患者在识别和吞噬凋亡细胞方面存在缺陷。如果死亡细胞不能被及时清除，它们会发生继发性坏死并释放核自身抗原。继发性坏死细胞来源的物质（SNEC）可以通过各种方法在体外生成。这两种方法生成的 SNEC 具有相似的 DNA 含量、光散射特征以及死亡和濒死细胞配体的结合模式，并且很容易被许多 SLE 患者的自身抗体（AAb）识别。在全血中，AAb 调理 SNEC 并促进其被血液来源的非专业吞噬细胞摄取。我们观察到吞噬了不同类型调理 SNEC 的吞噬细胞显著分泌了炎症细胞因子 IL-8 和 TNF-α。由于 DNA 酶 I 处理减少了 SNEC 的摄取和 IL-8 和 TNF-α 产生的诱导，因此 SNEC 的吞噬作用和随后的炎症细胞因子的产生强烈受到这种猎物中 DNA 存在的影响。总之，循环吞噬细胞对 IgG 调理的细胞碎片的促炎吞噬作用促进了 SLE 中的全身炎症。
