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From the * Renal Section, 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.
Department of
Medicine and § Department of Biochemistry, Boston University Medical Center Hospital, Boston,
Massachusetts 02118;
Department of Medicine and Therapeutics, University College Dublin, Mater
Miseracordiae, Dublin 7, Ireland; ¶ Renal Division, Department of Medicine, Brigham and Women's
Hospital, and the Renal Section, Medical Service, Brockton-West Roxbury Department of Veterans
Affairs Medical Center, Harvard Medical School, Boston, Massachusetts 02132; ** Laboratories of
Electron Microscopy and Structural Molecular Biology, Dana Farber Cancer Institute, and Department
of Cellular and Molecular Physiology, Harvard Medical School, Boston, Massachusetts 02132; and 
Division of Rheumatology, Montreal General Hospital Research Institute, McGill University,
Montreal, QC, Canada H3G 1A4
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