中性粒细胞细胞质抗原抗体诱导单核细胞分泌趋化蛋白-1。

B L Casselman, K S Kilgore, B F Miller, J S Warren
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引用次数: 0

摘要

在许多血管炎(如韦格纳肉芽肿病、小血管血管炎、特发性坏死性和新月性肾小球肾炎)患者的血清样本中发现了中性粒细胞胞浆抗原(ANCA)抗体。尽管在血清样本中检测ANCA已被证明是有用的诊断和在选定的疾病监测活动情况下,ANCA在血管炎中的发病作用仍然不明确。我们试图确定纯化的ANCA是否能促进分离的人外周血单核细胞分泌单核细胞趋化蛋白-1 (MCP-1)。P(核周)-和C(细胞质)- ANCA从韦格纳肉芽肿病、小血管炎或特发性坏死性和新月性肾小球肾炎患者的血清样本中纯化。健康人外周血单核细胞分别与C-ANCA免疫球蛋白G (IgG)、P-ANCA免疫球蛋白G或非特异性IgG孵育,并分析条件培养基中MCP-1的活性。单核细胞趋化试验用于功能性量化分泌的趋化活性。单核细胞趋化活性的分泌是抗体浓度依赖性和时间依赖性的,在添加C-或P-ANCA IgG后24小时收集的培养基中测量到最大的趋化性。针对人MCP-1的特异性抗体在很大程度上抑制了单核细胞趋化,表明MCP-1是条件培养基中主要的单核细胞趋化介质。MCP-1酶联免疫吸附实验进一步支持了P-和C-ANCA IgG可触发单核细胞分泌MCP-1的结论。这些数据表明,单核细胞与ANCA孵育促进了趋化β趋化因子MCP-1的剂量依赖性释放。(摘要删节250字)
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Antibodies to neutrophil cytoplasmic antigens induce monocyte chemoattractant protein-1 secretion from human monocytes.

Antibodies to neutrophil cytoplasmic antigens (ANCA) have been found in the serum samples of patients with a number of vasculitides (e.g., Wegener's granulomatosis, small vessel vasculitis, and idiopathic necrotizing and cresentic glomerulonephritis). Although detection of ANCA in serum samples has proven to be useful diagnostically and in selected activity of disease monitoring situations, the pathogenetic role of ANCA in vasculitis remains ill-defined. We sought to determine whether purified ANCA promotes the secretion of monocyte chemoattractant protein-1 (MCP-1) from isolated human peripheral blood monocytes. P (perinuclear)- and C (cytoplasmic)- ANCA were purified from the serum samples of patients with either Wegener's granulomatosis, small vessel vasculitis, or idiopathic necrotizing and cresentic glomerulonephritis. Human peripheral blood monocytes from healthy subjects were incubated with either C-ANCA immunoglobulin G (IgG), P-ANCA IgG, or nonspecific IgG, and the conditioned media were analyzed for MCP-1 activity. A monocyte chemotaxis assay was utilized to functionally quantify secreted chemotactic activity. Secretion of monocyte chemotactic activity was found to be antibody concentration-dependent and time-dependent, with maximal chemotaxis measured in media collected 24 hours after the addition of either C- or P-ANCA IgG. A specific antibody directed against human MCP-1 largely inhibited monocyte chemotaxis, indicating that MCP-1 is the predominant monocyte chemotactic mediator present in the conditioned medium. An MCP-1 enzyme-linked immunosorbent assay further supported the conclusion that P- and C-ANCA IgG can trigger MCP-1 secretion by monocytes. These data indicate that incubation of monocytes with ANCA promotes the dose-dependent release of the chemotactic beta-chemokine MCP-1.(ABSTRACT TRUNCATED AT 250 WORDS)

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