Antineutrophil cytoplasmic autoantibodies interact with primary granule constituents on the surface of apoptotic neutrophils in the absence of neutrophil priming.
Antineutrophil cytoplasmic autoantibodies interact with primary granule constituents on the surface of apoptotic neutrophils in the absence of neutrophil priming.
复制标题
DOI：
10.1084/jem.184.6.2231
复制
发表时间：
1996-12-01
影响因子：
15.3
通讯作者：
Levine, J S
中科院分区：
文献类型：
--
作者：
Gilligan, H M;Bredy, B;Brady, H R;Hebert, M J;Slayter, H S;Xu, Y;Rauch, J;Shia, M A;Koh, J S;Levine, J S
抗中性粒细胞胞浆自身抗体（ANCA）的致病作用仍然存在争议，因为很难解释细胞外ANCA如何与细胞内原代颗粒成分相互作用。据推测，中性粒细胞（PMN）的细胞因子启动，可能发生在前驱感染期间，是颗粒动员到细胞表面的重要触发因素，在那里它们可能与ANCA相互作用。我们通过电子显微镜显示，未引物PMN的凋亡也与细胞质颗粒向细胞表面的移位和在完整细胞膜下的排列有关。免疫荧光显微镜和FACS®分析显示，anca阳性血清和抗髓过氧化物酶抗体与凋亡的PMN反应性，但与活的PMN无反应性。此外，我们发现凋亡的PMN可以根据颗粒易位的存在或不存在分为两个亚群，并且髓过氧化物酶的表面免疫金标记仅发生在显示易位的PMN亚群中。这些结果提供了一种独立于启动的新机制，ANCA可能通过该机制在ANCA相关血管炎期间获得PMN颗粒成分。
The pathogenic role of antineutrophil cytoplasmic autoantibodies (ANCA) remains controversial because of the difficulty in explaining how extracellular ANCA can interact with intracellular primary granule constituents. It has been postulated that cytokine priming of neutrophils (PMN), as may occur during a prodromal infection, is an important trigger for mobilization of granules to the cell surface, where they may interact with ANCA. We show by electron microscopy that apoptosis of unprimed PMN is also associated with the translocation of cytoplasmic granules to the cell surface and alignment just beneath an intact cell membrane. Immunofluorescent microscopy and FACS® analysis demonstrate reactivity of ANCA-positive sera and antimyeloperoxidase antibodies with apoptotic PMN, but not with viable PMN. Moreover, we show that apoptotic PMN may be divided into two subsets, based on the presence or absence of granular translocation, and that surface immunogold labeling of myeloperoxidase occurs only in the subset of PMN showing translocation. These results provide a novel mechanism that is independent of priming, by which ANCA may gain access to PMN granule components during ANCA-associated vasculitis.