Mikołajczyk T P, Skiba D, Batko B, Krezelok M, Wilk G, Osmenda G, Pryjma J R, Guzik T J
Translational Medicine Laboratory, Department of Internal Medicine, Jagiellonian University School of Medicine, Cracow, Poland
Translational Medicine Laboratory, Department of Internal Medicine, Jagiellonian University School of Medicine, Cracow, Poland.
Lupus. 2014 Nov;23(13):1358-69. doi: 10.1177/0961203314541316. Epub 2014 Jun 26.
Efficient removal of apoptotic polymorphonuclear leukocytes (PMNs) is an important step in the resolution of inflammation, which protects tissues from the noxious contents of dying cells. While the impairment of apoptotic PMNs removal has been demonstrated for macrophages in systemic lupus erythematosus (SLE), recent studies show that monocytes are also capable of such phagocytosis, although their involvement in SLE is not clear. Therefore, we characterized phagocytosis of apoptotic PMNs by monocytes in 22 patients with SLE and 22 healthy controls. Using flow cytometry we demonstrate that in SLE peripheral blood monocytes show impaired phagocytosis of autologous apoptotic PMNs, while they efficiently engulf apoptotic PMNs isolated from healthy subjects. Monocytes CD14highCD16+ and CD14dimCD16+ more efficiently interacted with apoptotic neutrophils than CD16- cells both in SLE and healthy subjects. Monocytes in SLE showed modestly decreased expression of CD35 and CD91 and increased expression of T Cell Ig- and mucin-domain-containing molecule-3 (TIM-3); however, these differences were evident mainly in selected subsets of monocytes (CD16+) while defects in phagocytosis were observed in all monocyte subsets. Apoptotic cell-dependent induction of lipopolysaccharide (LPS) stimulated production of anti-inflammatory cytokine IL-10 by peripheral blood mononuclear cells (PBMC) was blunted in SLE while the production of pro-inflammatory cytokine TNF-α was unchanged.
有效清除凋亡的多形核白细胞（PMN）是炎症消退的重要步骤，可保护组织免受死亡细胞有害内容物的影响。虽然系统性红斑狼疮（SLE）患者巨噬细胞清除凋亡PMN的功能受损已得到证实，但最近的研究表明，单核细胞也具有这种吞噬能力，尽管它们在SLE中的作用尚不清楚。因此，我们对22例SLE患者和22例健康对照者单核细胞对凋亡PMN的吞噬作用进行了表征。通过流式细胞术，我们证明在SLE患者中，外周血单核细胞对自体凋亡PMN的吞噬功能受损，而它们能有效吞噬从健康受试者分离的凋亡PMN。在SLE患者和健康受试者中，CD14highCD16+和CD14dimCD16+单核细胞比CD16-细胞更有效地与凋亡中性粒细胞相互作用。SLE患者的单核细胞CD35和CD91表达略有下降，含T细胞免疫球蛋白和粘蛋白结构域分子-3（TIM-3）的表达增加；然而，这些差异主要在单核细胞的特定亚群（CD16+）中明显，而在所有单核细胞亚群中均观察到吞噬功能缺陷。SLE患者外周血单个核细胞（PBMC）中脂多糖（LPS）刺激产生抗炎细胞因子IL-10的凋亡细胞依赖性诱导作用减弱，而促炎细胞因子TNF-α的产生未改变。
