Suzuki K
Laboratory of Biodefence, National Institute of Infectious Diseases (NIID-NIH), Tokyo, Japan.
Int J Hematol. 2001 Aug;74(2):134-43. doi: 10.1007/BF02981995.
Neutrophils are hypothesized to cause tissue damage resulting in the development of vasculitis and glomerulonephritis, although they are known to primarily take part in host defense functions. The infiltration of inflammatory cells. notably neutrophils and macrophages, is observed in the progression of vasculitis. Neutrophils with activated status and anti-neutrophil cytoplasmic antibodies (ANCAs), especially myeloperoxidase-specific (MPO)-ANCA, have been implicated in the development of vasculitis. The target molecule of MPG-ANCA is a lysosomal enzyme MPO that usually acts to kill bacteria, viruses, and fungi and that causes damage to the tissue due to the toxicity of its product, hypochlorite (OCl-). To elucidate the role of MPO-ANCA in the progression of vasculitis, a set of MPO-peptide fragments has been developed, and the corresponding epitope site for the specific monoclonal and/or oligoclonal antibody resulting in vasculitis has been determined. Recently some mouse models have been used for analyzing the correlation between MPO and MPO-ANCA in relation to damage of blood vessels followed by the development of vasculitis. This review focuses on the role of activated neutrophils in the development of vasculitis associated with MPO-ANCA and the target molecules of ANCA. In addition, the reactivities of ANCA and inflammatory cytokines involving leukocyte-derived chemotaxin 2 (LECT2) are also discussed.
尽管已知中性粒细胞主要参与宿主防御功能,但据推测它们会导致组织损伤,进而引发血管炎和肾小球肾炎。在血管炎的进展过程中可观察到炎性细胞浸润,尤其是中性粒细胞和巨噬细胞。活化状态的中性粒细胞和抗中性粒细胞胞浆抗体(ANCA),特别是髓过氧化物酶特异性(MPO)-ANCA,与血管炎的发生有关。MPG-ANCA的靶分子是溶酶体酶MPO,它通常作用于杀灭细菌、病毒和真菌,并因其产物次氯酸盐(OCl-)的毒性而对组织造成损伤。为阐明MPO-ANCA在血管炎进展中的作用,已开发出一组MPO肽片段,并确定了导致血管炎的特异性单克隆和/或寡克隆抗体的相应表位位点。最近,一些小鼠模型被用于分析MPO与MPO-ANCA之间的相关性,这种相关性与血管损伤继而发生血管炎有关。本综述重点关注活化中性粒细胞在与MPO-ANCA相关的血管炎发生中的作用以及ANCA的靶分子。此外,还讨论了ANCA与包括白细胞衍生趋化因子2(LECT2)在内的炎性细胞因子的反应性。