Induction of biologically active antineutrophil cytoplasmic antibodies by immunization with human apoptotic polymorphonuclear leukocytes

Induction of biologically active antineutrophil cytoplasmic antibodies by immunization with human apoptotic polymorphonuclear leukocytes
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DOI:
10.1006/clim.2002.5194
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发表时间:
2002-04-01
影响因子:
8.6
通讯作者:
Shoenfeld, Y
Shoenfeld, Y
中科院分区:
医学3区
文献类型:
--
作者:
Rauova, L;Gilburd, B;Shoenfeld, Y

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在多形核白细胞 (PMN) 的启动或凋亡过程中,细胞内成分易位至细胞表面是抗中性粒细胞胞浆抗体 (ANCA) 与这些抗原相互作用的重要机制。为了测试凋亡的 PMN 触发 ANCA 产生的能力,用活的或凋亡的淋巴细胞,或者用活的、凋亡的、福尔马林固定的或裂解的 PMN 免疫六组小鼠。用活的和凋亡的中性粒细胞免疫的小鼠产生高滴度的抗体,产生颗粒状细胞质免疫荧光模式。这些抗体对乳铁蛋白和髓过氧化物酶具有特异性。第二次静脉注射凋亡性中性粒细胞后,小鼠产生了抗 PR3 抗体。在发生 ANCA 的小鼠中未发现血管炎病变。含有 ANCA 的 IgG 部分诱导人类 PMN 产生超氧化物。这些结果支持这样的假设:凋亡性 PMN 细胞膜上呈递的中性粒细胞特异性抗原可能在适当的条件下诱导 ANCA。 (C) 2002 年爱思唯尔科学(美国)。
Translocation of intracellular components to the cell surface during the priming or apoptosis of polymorphonuclear leukocytes (PMN) is an important mechanism for interaction of antineutrophil cytoplasmic antibodies (ANCA) with these antigens. To test the capacity of apoptotic PMN to trigger production of ANCA, six groups of mice were immunized with either live or apoptotic lymphocytes, or with live, apoptotic, formalin-fixed, or lysed PMN. Mice immunized with both live and apoptotic neutrophils developed high titers of antibodies which gave a granular cytoplasmic immunofluorescent pattern. These antibodies were specific for lactoferrin and myeloperoxidase. Following a second intravenous infusion of apoptotic PMNs, mice developed anti-PR3 antibodies. Vasculitis lesions were not found in mice which developed ANCA. The ANCA-containing IgG fraction induced superoxide production by human PMNs. These results support the hypothesis that neutrophil-specific antigens presented on the cell membranes of apoptotic PMN may induce ANCA in the proper conditions. (C) 2002 Elsevier Science (USA).