抗中性粒细胞胞浆自身抗体(ANCA)血管炎具有多种损伤模式,包括显微镜下多血管炎(MPA),肉芽肿性多血管炎(GPA),和嗜酸性肉芽肿性多血管炎(EGPA)。坏死性和新月体肾小球肾炎(NCGN)发生在所有综合征中,并作为肾限制性血管炎(RLV)。对小鼠髓过氧化物酶(MPO)特异性的单剂量静脉内ANCAIgG在小鼠中引起RLV。尽管多种小鼠模型已经阐明了ANCA-IgG诱导的坏死性和新月体肾小球肾炎(NCGN),ANCA诱导的肉芽肿病和肾外血管炎的发病机制尚未阐明。为了调查这一点,我们在同一品系小鼠中使用静脉MPO-ANCAIgG诱导不同类型的肺部疾病,反映肉芽肿性多血管炎(GPA)患者,显微镜下多血管炎(MPA),和嗜酸性肉芽肿性多血管炎(EGPA)。反复静脉注射MPO-ANCAIgG诱导的GPA与NCGN,肺毛细血管炎,动脉炎和肉芽肿。通过免疫组织化学图像分析和流式细胞术评估肺白细胞表型。ANCA肺毛细血管炎和微脓肿在一天内开始,并在七天内演变成肉芽肿。流感加单剂量MPO-ANCAIgG诱导的MPA与NCGN,肺毛细血管炎和动脉炎,但没有肉芽肿病.由屋尘螨或卵清蛋白加上单剂量静脉注射MPO-ANCAIgG引起的EGPA伴嗜酸性细支气管炎引起的过敏性气道疾病,NCGN,毛细血管炎,动脉炎,和肉芽肿病.因此,我们的研究表明,肺部病变的发生和模式是由相同的ANCAIgG伴随不同的协同免疫因子决定的。
Anti-neutrophil cytoplasmic autoantibody (
ANCA) vasculitis has diverse patterns of injury including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Necrotizing and crescentic glomerulonephritis (NCGN) occurs in all syndromes and as renal limited vasculitis (RLV). Single dose intravenous
ANCA IgG-specific for mouse myeloperoxidase (MPO) causes RLV in mice. Although multiple mouse models have elucidated ANCA-IgG induced necrotizing and crescentic glomerulonephritis (NCGN), pathogenesis of ANCA-induced granulomatosis and vasculitis outside the kidney has not been clarified. To investigate this, we used intravenous MPO-
ANCA IgG in the same strain of mice to induce different patterns of lung disease mirroring patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Repeated intravenous MPO-ANCA IgG induced GPA with NCGN, lung capillaritis, arteritis and granulomatosis. Lung leukocyte phenotypes were evaluated by immunohistochemical image analysis and by flow cytometry. ANCA lung capillaritis and microabscesses began within one day and evolved into granulomas in under seven days. Influenza plus single dose MPO-ANCA IgG induced MPA with NCGN, lung capillaritis and arteritis, but no granulomatosis. Allergic airway disease caused by house dust mites or ovalbumin plus single dose intravenous MPO-
ANCA IgG induced EGPA with eosinophilic bronchiolitis, NCGN, capillaritis, arteritis, and granulomatosis. Thus, our study shows that the occurrence and pattern of lung lesions are determined by the same
ANCA IgG accompanied by different synergistic immune factors.